Programmed cell death protein 1 is a marker for neoadjuvant chemotherapy response in triple-negative breast cancer

SUMMARY OBJECTIVE: Tumor-infiltrating lymphocytes are detectable in up to 75% of triple-negative breast cancer. The composition of these infiltrates may influence prognosis and is not known regarding regulatory or effector lymphocytes. The objectives of this study were to describe and quantify the composition of the tumor-infiltrating lymphocytes before and after chemotherapy (neoadjuvant chemotherapy) and to evaluate their association with complete pathological response and overall survival. METHODS: This was a retrospective observational study. Clinical and pathological data from 38 triple-negative breast cancer patients treated with neoadjuvant chemotherapy at the University Hospital (HUCFF/UFRJ), between November 2004 and November 2018, were analyzed. The Stromal tumor-infiltrating lymphocytes (Stromal tumor-infiltrating lymphocytes) have been identified on hematoxylin and eosin-stained sections according to the guidelines of the "International tumor-infiltrating lymphocytes Working Group." Immunohistochemistry studies were performed to identify T-cell subsets (i.e., CD3, CD4, CD8, and FOXP3) and T-cell exhaustion (i.e., programmed cell death protein 1). RESULTS: Statistically significant changes in stromal tumor-infiltrating lymphocyte categories were observed before and post-neoadjuvant chemotherapy, with 32% of intermediate cases becoming high. The correlation between pre-neoadjuvant chemotherapy stromal tumor-infiltrating lymphocytes and pathological response, pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy, and stromal tumor-infiltrating lymphocytes and overall survival was not statistically significant. However, we noticed an increase of cells that favor the antitumor activity (i.e., CD3, CD8, and CD8/FOXP3 ratio) and decreased levels of cells inhibiting tumor activities (i.e., FOXP3 and programmed cell death protein 1) post-neoadjuvant chemotherapy. Importantly, programmed cell death protein 1 expression pre-neoadjuvant chemotherapy showed an association with pathological response. CONCLUSION: In this study, we observed that chemotherapy significantly increases stromal tumor-infiltrating lymphocytes, CD8 T cells, as well as CD8/FoxP3 ratio. Most importantly, programmed cell death protein 1 expression before neoadjuvant chemotherapy positively correlates with pathological response suggesting the use of programmed cell death protein 1 as a prognostic marker before neoadjuvant chemotherapy.

Tumoral inflammatory infiltrate does not predict metastases in thin primary cutaneous melanomas

Abstract Background In cutaneous melanomas in general, tumor inflammatory infiltrate (TII) can protect against distant metastases, but there is no consensus when only thin primary cutaneous melanomas (TPCM) are considered. Objective To investigate the presence of TII in TPCM and the relationship between TII and the occurrence of metastases. Methods Case-control study including 50 patients with TPCM, 22 metastatic (MC group) and 28 non-metastatic (NMC group). The presence of TII was evaluated and, if present, qualified as mild, moderate or marked. Results The mean age was 50.7 years in the MC and 56.2 years in the NMC group (p = 0.234), and the male sex predominated in the MC group (63.6%). The average Breslow thickness was higher in the MC when compared to that observed in the NMC (respectively 0.8 vs. 0.6 mm, p = 0.012). The presence of ulceration occurred in 22.7% of the MC and 17.9% of the NMC (p = 0.732). TII was present in all 50 TPCM, being marked or moderate in 67.9% of the NMC and 54.5% in the MC group (p = 0.503). In the multivariate analysis, the presence of moderate and marked TII had an Odds Ratio (OR) of 0.57 (95% Confidence Interval [CI]: 0.18‒1.8) and adjusted OR of 0.68 (95% CI 0.13‒3.99). Study limitations Small sample size. Conclusions TII was present in all TPCM (with and without metastases), and it was not possible to demonstrate a protective effect of TII against the appearance of metastases.

Research advances in tumor-infiltrating lymphocytes in treatment of biliary tract cancer / 临床肝胆病杂志

Tumor-infiltrating lymphocytes (TILs) are a heterogeneous subset of lymphocytes, mainly T cells, present in tumor parenchyma and stroma. After being digested and isolated from tumor tissue and then cultured in vitro for activation and multiplication, it can be infused back into the patient's body to kill tumor cells. TILs have the advantages of high diversity of TCR, excellent ability to infiltrate into tumor sites, and low toxicity and are considered promising for the treatment of malignant solid tumors. At present, TIL therapy has been tested as a second-line treatment in a variety of solid tumors and has achieved preliminary results. Although there is still no clinical cohort report on the application of TILs in biliary tract cancer (BTC), recent clinical reports on multiple cancers have provided information on the efficacy of TIL therapy in a small number of BTC patients, which preliminarily confirmed the safety and efficacy of TIL therapy. However, since BTC is generally considered an immunologically repulsive tumor in which most effector T cells are sequestered at the tumor edge, the antitumor effect of TILs in BTC remains difficult to predict. Combination therapy with different anti-tumor methods and the development of new techniques to modify cells to enhance the anti-tumor ability of TILs are possible directions for breakthrough in the future.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Clinical significance of CD8 positive tumor-infiltrating lymphocytes density and programmed-death receptor ligand 1 expression in rectal cancer after neoadjuvant chemoradiotherapy / 肿瘤研究与临床

Objective:To investigate the correlation of CD8 positive tumor-infiltrating lymphocytes (CD8 + TIL) density and programmed-death receptor ligand 1 (PD-L1) expression in rectal cancer with clinicopathological characteristics and prognosis of patients after neoadjuvant chemoradiotherapy. Methods:The clinicopathological data of 166 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgery in the Beijing Chao-Yang Hospital, Capital Medical University from January 2015 to December 2018 were retrospectively analyzed. CD8 + TIL density and PD-L1 expression were detected by using immunohistochemistry. The correlation of CD8 + TIL density and PD-L1 expression with clinicopathological characteristics of patients after neoadjuvant chemoradiotherapy was analyzed. Kaplan-Meier method was used to analyze the disease-free survival (DFS) and Cox regression risk model was used to make univariate and multivariate analysis of the influencing factors for DFS. Results:Among 166 LARC patients, 81 cases (48.8%) had high density of CD8 + TIL, 85 cases (51.2%) had low density of CD8 + TIL; 63 cases (38.0%) had PD-L1 expression, and 103 cases (62.0%) had non-expression of CD8 + TIL. The expression rate of PD-L1 in CD8 + TIL high density group was higher than that in CD8 + TIL low density group [50.6% (41/81) vs. 25.9%(22/85), χ2 = 10.78, P < 0.001]. According to the density of CD8 + TIL and PD-L1 expression, immunophenotype was divided among 4 groups; the 3-year DFS rate of the CD8 + TIL high density /PD-L1 expression group was 87.1%, which was higher than that of the other groups (CD8 + TIL low density /PD-L1 expression group was 72.8%, CD8 + TIL high density /PD-L1 non-expression group was 67.0%, CD8 + TIL low density /PD-L1 non-expression group was 64.3%), and the difference was statistically significant ( P < 0.05). Univariate analysis showed that tumor differentiation degree, TNM stage, CD8 + TIL density, PD-L1 expression and CD8 + TIL density /PD-L1 expression were correlated with the DFS of patients (all P < 0.05). Multivariate analysis results showed that CD8 + TIL high density /PD-L1 expression was an independent protective factor for DFS ( HR = 0.049, 95% CI 0.005-0.497, P = 0.011), while TNM stage 3 was an independent risk factor for DFS ( HR = 2.752,95% CI 1.300-5.825, P = 0.008). Conclusions:In LARC after neoadjuvant therapy, CD8 + TIL density is positively correlated with the expression of PD-L1, and the high density of CD8 + TIL/PD-L1 expression is an independent influencing factor for good prognosis, suggesting that these patients may benefit from the immunotherapy.

Application of deep learning to the differenciation of the invasion depth in colorectal adenomas / 中华消化内镜杂志

Objective:To evaluate deep learning for differentiating invasion depth of colorectal adenomas under image enhanced endoscopy (IEE).Methods:A total of 13 246 IEE images from 3 714 lesions acquired from November 2016 to June 2021 were retrospectively collected in Renmin Hospital of Wuhan University, Shenzhen Hospital of Southern Medical University and the First Hospital of Yichang to construct a deep learning model to differentiate submucosal deep invasion and non-submucosal deep invasion lesions of colorectal adenomas. The performance of the deep learning model was validated in an independent test and an external test. The full test was used to compare the diagnostic performance between 5 endoscopists and the deep learning model. A total of 35 videos were collected from January to June 2021 in Renmin Hospital of Wuhan University to validate the diagnostic performance of the endoscopists with the assistance of deep learning model.Results:The accuracy and Youden index of the deep learning model in image test set were 93.08% (821/882) and 0.86, which were better than those of endoscopists [the highest were 91.72% (809/882) and 0.78]. In video test set, the accuracy and Youden index of the model were 97.14% (34/35) and 0.94. With the assistance of the model, the accuracy of endoscopists was significantly improved [the highest was 97.14% (34/35)].Conclusion:The deep learning model obtained in this study could identify submucosal lesions with deep invasion accurately for colorectal adenomas, and could improve the diagnostic accuracy of endoscopists.

Can TILs be associated with prognostic factors and survival rates in breast cancer? A retrospective analysis

Introduction: The relationship between the tumor inflammatory infiltrate, also known as tumor-infiltrating lymphocytes (TILs), and invasive breast carcinomas has been extensively studied in recent years to verify its association with prognosis and response to treatment. The goal of this study was to associate the presence of TILs with patient's survival time. Methods: We studied prognostic clinicopathological characteristics already established in the literature and their impact on overall five-year survival time of patients with invasive breast cancer treated at Hospital Santa Casa in Belo Horizonte, Minas Gerais, Brazil, in 2011 (n=290). This was an observational and retrospective study. Results: The presence of TILs was associated with tumors of no special type (p=0.018) and with younger age of the patients (p=0.042). Smaller tumor size (HR: 19.24; 95%CI 4.30­86.15; p<0.001), absence of metastasis to the axillary lymph nodes (HR: 2.80; 95%CI 1.02­7.70; p=0.002), positivity for progesterone receptor (HR: 0.39; 95%CI 0.17­0.87; p=0.022), and presence of TILs (HR: 0.23; 95%CI 0.08­0.65; p=0.005) were associated with longer survival times. Conclusions: This study suggests that the presence of TILs, along with other clinicopathological characteristics, is a prognostic factor in breast cancer

CD45RO+TILs: cellular biomarkers for larynx squamous cell carcinoma outcome

Abstract Objective: The prognostic importance of Tumor-Infiltrating Lymphocytes (TILs) in the tumor microenvironment of various cancers is increasingly recognized. In the present study, we aimed to investigate the prognostic value of CD3+, CD4+, CD8+, and CD45RO + TILs and their relation to histopathological features in larynx squamous cell carcinoma. Methods: Formalin-Fixed and Paraffin-Embedded (FFPE) samples from 63 primary larynx squamous cell carcinoma patients were immunostained for CD3, CD4, CD8, and CD45RO expression. Positive cells in micrographs from Invasive Margin (IM) and Tumor Center (CT) of tissue specimens counted by ImageJ software and their correlation with disease outcome were analyzed. Results: The expression level of TILs subpopulations was associated with clinicopathological markers as well as Overall Survival (OS) and Disease-Free Survival (DFS). In multivariate analysis, high frequency of CD45RO + cells in IM were confirmed as an independent prognostic marker for DFS (p = 0.007, HR = 4.968) and OS (p = 0.007, HR = 4.957). Similar findings were observed in the multivariate analysis of the combined frequency of CD45RO+cells in IM and CT. Conclusion: TILs are associated with patients clinicopathological features. Also, our findings indicate that CD45RO + TILs are a valuable marker for risk prediction in larynx SCC and could predict patients' outcomes.

Is there any correlation between tumor infiltrating lymphocytes and expression of EGFR in squamous cell carcinoma of head and neck? A retrospective observational study

Background: The dismal survival of one of the commonest malignancies of the world, head neck squamous cell carcinomas (HNSCC), has prompted researchers to probe into its various characteristics, especially those which reflect the outcome. Over the years, even though epidermal growth factor receptor (EGFR) and tumor-infiltrating lymphocytes (TIL) have emerged as useful biomarkers of the disease, the two parameters have rarely been considered in conjunction. Aims and Objectives: The study aimed to assess if there is any correlation between TIL levels (both stromal and intratumoral) and site, grade, stage, and EGFR score of HNSCC. Materials and Methods: A retrospective observational study was conducted in which histopathologically confirmed cases of HNSCC were included. The site of tumor, grade, stage, stromal and intratumoral TIL levels, and EGFR score were noted for each case. The data were analyzed using standard statistical tests. Results: The study population consisted of 122 patients with a mean age of 53.8 ± 9.2 years. The oral cavity was the commonest site of tumor (109 cases, 89.3%). Most cases were moderately differentiated (75, 61.5%). Pathological staging showed 66 cases (54%) to be in pT1, and 92 cases (75.4%) to be in pN0. In 68 cases (55.7%), stromal TIL level was high, and intratumoral TIL was low in 102 cases (83.6%). A statistically significant correlation was found between TIL levels and site, grade, pathological stage, and EGFR score of HNSCC. Conclusion: This pioneering study is unique in its exploration of the correlation between two significant biomarkers of HNSCC – TIL and EGFR score.

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma

Abstract Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Research progress of different tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer / 中华内分泌外科杂志

Triple-negative breast cancer is considered to be the most aggressive subtype of breast cancer. Due to its lack of expression of estrogen receptor (ER) , progesterone receptor (PR) and HER-2, there is still a lack of clear prognostic judgments and biomarkers that guide treatment. With the development of tumor immunology, the relationship between tumor immune microenvironment and tumor occurrence and development has gradually gained attention. More and more evidence suggests that the higher the level of tumor-infiltrating lymphocytes (TIL) infiltration in triple-negative breast cancer lesions, the better the prognosis of patients. However, TIL is not a single type of cell, and its different lymphocyte subpopulations have different prognostic effects in patients with triple-negative breast cancer. This article summarizes the relationship between different immune cell subgroups in the tumor immune microenvironment and the prognosis of TNBC patients.

Establishment of a prediction model for colorectal cancer immune cell infiltration based on the cancer genome atlas (TCGA) database / 北京大学学报(医学版)

OBJECTIVE@#To study the correlation between immune cell infiltration in colorectal cancer tissue and clinical prognosis and to explore the levels of some immune cell genes for predicting the prognosis of patients with glioma colorectal cancer.@*METHODS@#In this study, we extracted colorectal cancer data from the cancer genome atlas (TCGA). Based on a deconvolution algorithm (called CIBERSORT) and clinically annotated expression profiles, the analysis assessed the infiltration patterns of 22 immune cells in colorectal cancer tissue to determine the association between each cell type and survival. Differences in five-year survival rate effectively illustrate the clinical prognostic value of each immune cell proportion in colorectal cancer, using a bar graph, correlation-based heatmap to represent the proportion of immune cells in each colorectal cancer sample.@*RESULTS@#A total of 473 colorectal cancer tissues and 41 normal control tissues were extracted from the TCGA database, and the comparative analysis showed that there were differences in the proportion of various TIICs in colorectal cancer tissues, which could characterize individual differences and have prognostic value. Among the cell subsets studied, the proportions of memory B cells, plasma cells, CD4+ T cells, natural killer (NK) cells, M0 macrophages, M2 macrophages, and activated mast cells were significantly different between normal and cancer tissues. Resting NK cells, CD8+ T cells, and plasma cells were associated with T phase, activated dendritic cells were associated with N phase, and eosinophils, M1 macrophages, and activated mast cells were associated with M phase. Survival analysis showed that activated dendritic cells were positively associated with five-year survival rate in colorectal cancer patients. Naive CD4+ T cells were inversely associated with five-year survival rate.@*CONCLUSION@#There are different degrees of immune cell infiltration in colorectal cancer tissues, and these differences may be important determinants of prognosis and treatment response. We conducted a new gene expression-based study of immune cell subtype levels and prognosis in colorectal cancer, which has potential clinical prognostic value in colorectal cancer patients.

SPECT/CT imaging of tumor-infiltrating CD8 + T cell to predict the efficacy of anti-PD-1 immunotherapy in mice / 中华核医学与分子影像杂志

Objective:To prepare 99Tc m-hydrazinonicotinamide(HYNIC)-αCD8/Fab ( 99Tc m-αCD8/Fab), and explore the predictive value of 99Tc m-αCD8/Fab SPECT/CT imaging for the efficacy of anti-programmed death-1 (PD-1) immunotherapy. Methods:The αCD8/Fab was modified with HYNIC- N-hydroxysuccinimide (NHS) and IRDye800-NHS to form HYNIC-αCD8/Fab and IRDye800-αCD8/Fab (Dye-αCD8/Fab), respectively. 99Tc m-αCD8/Fab was prepared in sodium bicarbonate buffer (pH=8.5), with SnCl 2 being used as the reducing agent. The labeling yield and radiochemical purity of 99Tc m-αCD8/Fab and its stability in PBS and fetal bovine serum (FBS) were tested in vitro. The mouse spleen and human peripheral blood lymphocytes were isolated for cell-specific binding and blocking experiments of 99Tc m-αCD8/Fab in vitro. SPECT/CT imaging was used to analyze the specific binding ability of the 99Tc m-αCD8/Fab probe in CT26 colon cancer mouse models (BALB/c). The near infrared fluorescence imaging and SPECT/CT imaging were performed to detect the intra-tumoral CD8 + T cell infiltration after anti-PD-1 therapy in tumor bearing mice, and the results were further verified by HE and immunofluorescence staining. CD8 + T cell depletion study was performed to determine the role of CD8 + T cells in the tumor responses to anti-PD-1 therapy. Two-way analysis of variance was used to compare the data difference. Results:The labeling yield of 99Tc m-αCD8/Fab was 90% with a high radiochemical purity (95%) and good stability in vitro (radiochemical purity still more than 80% after 720 min in PBS and FBS). 99Tc m-αCD8/Fab could specifically bind to mouse CD8 + T cells ((10.30±0.81) percent added radioactive dose (%AD)/10 6 cells), compared with the binding ability in human peripheral blood lymphocytes group and CD8 antibody blocking group ((1.78±0.61) and (1.59±0.25) %AD/10 6 cells; F=10.07, P<0.001). SPECT/CT imaging showed that 99Tc m-αCD8/Fab had markedly higher tumor uptake in the CT26 colon cancer mouse models. Near-infrared fluorescence imaging showed that the tumor uptake of 99Tc m-αCD8/Fab in the responsive group was significantly higher than in the nonresponsive group after anti-PD-1 treatment ((8.9±1.1)% vs (7.1±0.8)%; F=4.69, P=0.024), and SPECT/CT imaging found the similar result. HE and immunofluorescence staining of tumor and lymph nodes showed that the proportion of lymphocyte infiltration was higher in the responsive group. Furthermore, CD8 + T cell depletion significantly reversed the therapeutic effect of anti-PD-1 immunotherapy in tumor-bearing mice. Conclusions:In this study, 99Tc m-αCD8/Fab was successfully obtained. CD8-specific SPECT imaging could sensitively visualize the tumor-infiltrating CD8 + T cells, suggesting the potential application value to predict and evaluate the efficacy of immunotherapy in the clinical settings.

Progress on Tumor Infiltrating Lymphocytes in Immunotherapy and Prognosis Evaluation of Breast Cancer / 肿瘤防治研究

Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer in 2020. A large number of studies have proved that tumor infiltrating lymphocytes (TILs) are lethal to tumors and play an important role in identifying tumor antigens. Therefore, the application of TILs in clinical immunotherapy and prognosis assessment of breast cancer has attracted wide attention. In this review, the basic research progress and clinical application of TILs in different molecular types of breast cancer are reviewed, and the value of TILs in judging breast cancer prognosis and predicting the therapeutic effect of clinical immunotherapy is evaluated.

Expression of FGL2 in Colon Cancer and its Clinical Significance / 胃肠病学

Background: Colorectal cancer is one of the most commonly diagnosed cancer and leading causes of cancer death worldwide. Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen family, has been demonstrated as a regulator of immune cell functions in tumor microenvironment and might facilitate tumor progression. Aims: To study the expression and clinical significance of FGL2 in colon cancer. Methods: One hundred and fifty colon cancer patients diagnosed from January 2018 to January 2022 at the Second Hospital of Tianjin Medical University were enrolled in this study. The paraffin-embedded tissues were collected for detection of FGL2 protein and the surface markers of tumor infiltrating immune cells (TIICs), including CD4, CD8, CD20, CD68, and CD56 by using immunohistochemistry. The correlations of FGL2 expression level with the clinicopathological parameters and TIICs counting were analyzed. Results: Expression of FGL2 was upregulated in 68.7% of the colon cancer cases. Its expression level was correlated positively with the tumor size and TNM staging (all P0.05). Meanwhile, the expression level of FGL2 was associated with the cell counting of CD4

Effects of Shenqi fuzheng injection on low-glucose-mediated immunosuppressive microenvironment and its mechanism of action / 中国临床药理学与治疗学

AIM: To investigate the effect of Shenqi fuzheng injection (SFI) on tumor immunity and its preliminary molecular mechanism. METHODS: The animal model of low glucose tumor microenvironment was established by B16-PKM2-OE; the level of interleukin-2(IL-2) and interferon-γ(IFN-γ), CD40L and transforming growth factor-β1(TGF-β1) were detected by ELISA kit; the expressions of glucose transporter-1 (Glut-1) and key enzymes of glycolysis ( HK, PFK and PK ) in CD4

Research Status of Tumor-associated Fibroblasts Regulating Immune Cells / 中国肺癌杂志

Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment.
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Progress of Tumor Infiltrating Lymphocytes in Immunotherapy of Triple Negative Breast Cancer / 中国医学科学院学报

Breast cancer has become the most common cancer for women in China.Lack of effective therapeutic targets,triple negative breast cancer(TNBC)has poorer prognosis compared with other subtypes of breast cancer.Tumor infiltrating lymphocytes(TILs)are a group of heterogeneous lymphocytes around the tumor,which are believed as immunoreactive products of host immune response to tumor antigens.At present,there have been reports on the predictive effect of TILs on the prognosis of breast cancer,and the available studies focus mainly on TNBC.This article briefly reviews the recent progress of tumor infiltrating lymphocytes in immunotherapy of TNBC.

Systematic evaluation of the relationship between tumor-infiltrating lymphocytes and prognosis of triple negative breast cancer / 国际外科学杂志

Objective:To investigate the prognostic value of tumor infiltrating lymphocytes (TILs) and their phenotypes, CD4 + TILs, CD8 + TILs and FOXP3 + TILs, in short-term prognosis (PCR) and long-term prognosis (DFS, OS) of triple negative breast cancer (TNBC), and to provide theoretical support for the immunotherapy of TNBC. Methods:A systematic surch of PubMed, Medline, Embase, Web of Science, CBM, CNKI was conducted to identified eligible articles. All prospective trials and observational controlled trials published before August 2020 were retrieved.The two authors independently evaluated the quality of the included literature, extracted the data, and conducted systematic evaluation and analysis using RevMan5.3 software.Results:A total of 48 literatures were included.Every 10% increase in TILs and TILs expression in the high-expression group predicted a higher PCR, OR were 1.81 (95% CI: 1.44-2.28) and 1.09 (95% CI: 1.02-1.15). For longer survival, the HR for DFS and OS were 0.99 (95% CI: 0.98-0.99) and 0.90 (95% CI: 0.86-0.94), 0.87 (95% CI: 0.79-0.96) and 0.88 (95% CI: 0.83-0.92). Phenotypic CD4 + TILs, CD8 + TILs, and FOXP3 + TILs did not show statistically significant differences in PCR among patients, but in long-term prognosis, higher infiltration predicted longer survival, with HR for DFS of 0.54 (95% CI: 0.36-0.80), 0.46(95% CI: 0.33-0.64) and 0.45(95% CI: 0.31-0.68). HR of OS were 0.49 (95% CI: 0.32-0.76), 0.59 (95% CI: 0.54-0.66) and 0.44 (95% CI: 0.27-0.71). Conclusion:The infiltration degree of TILs and the increase of TILs expression by 10% can be used as a prognostic index of TNBC.High levels of phenotypic infiltration of CD4 + TILs, CD8 + TILs, and FOXP3 + TILs predicted better long-term survival, but there was no statistically significant difference in short-term survival.

Comprehensive analysis of the association between tumor-infiltrating immune cells and the prognosis of lung adenocarcinoma

Context: Increasing evidence has indicated an association between immune cell infiltration in lung adenocarcinoma (LUAD) and clinical outcomes. Aims: This study aimed to investigate the effect of 22 tumor-infiltrating immune cells (TIICs) on the prognosis of patients with LUAD. Settings and Design: This was a case–control study. Materials and Methods: The CIBERSORT algorithm calculated the proportion of cases from the Cancer Genome Atlas (TCGA) cohort. Cox regression analysis evaluated the effect of TIICs on the prognosis of LUAD. The immune risk score model was constructed based on a statistical correlation. Multivariate cox regression analysis investigated independent factors. P < 0.05 was considered to be statistically significant. Results: Certain immune cells had differential infiltration between normal tissues and LUAD. Univariate Cox regression analysis revealed that four immune cell types were statistically correlated with LUAD-related survival risk, and an immune risk scoring model was constructed. The results indicated that patients in the high-risk group were associated with poor outcomes. In addition, the multivariate cox analysis revealed that the immune risk scoring model was an independent factor for LUAD prognosis prediction. Ultimately, a nomogram was established to comprehensively predict the survival of LUAD patients. Conclusions: TIICs played an essential role in the prognosis of LUAD. Furthermore, the immune risk score was a poor predictive factor of LUAD, and the established model was reliable in predicting the prognosis of LUAD