Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients.

T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI+) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3+IFNγ+ cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI+ T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI+ patients compared to PreI- patients (not reached vs. 321 days, respectively; p = 0.014). PreI+ patients had significantly higher numbers of possible exhausted CD3+CD8+PD-1+ cells and lower percentages of immunosuppressive Tregs compared to PreI- patients. Additionally, patients with PreI+ and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens.

ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment.

SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express PD-L1 in treatment-naïve ES-SCLC patients receiving ICI in a front-line setting. Moreover, we explored the percentages of different immune T-cell subsets in circulation to assess their potential role in predicting responses. A total of 43 patients were enrolled-6 of them with LS-SCLC, and 37 with ES-SCLC disease. In addition, PBMCs from 10 healthy donors were used as a control group. Different T-cell subtypes were examined through multicolor FACS analysis and patients' CTCs were detected using immunofluorescence staining. SCLC patients had higher percentages of PD-1-expressing CD3+CD4+ and CD3+CD8+ T-cells, as well as elevated PD-1 protein expression compared to healthy individuals. Additionally, in ES-SCLC patients, a positive correlation between CD3+CD8+PD-1+ T-cells and PD-L1+ CTCs was detected. Importantly, patients harboring higher numbers of CD3+CD8+PD-1+ T-cells together with PD-L1+CTCs had a survival advantage when receiving front-line immunotherapy. Thus, this study proposes, for first time possible, immune cell-CTCs interaction, as well as a potential novel clinical biomarker for ICI responses in ES-SCLC patients.

Successful Shrinkage of a Giant Cutaneous Squamous Cell Carcinoma with Immunotherapy in a Kidney Transplant Recipient.

A 56-year-old male living donor kidney transplant recipient presented with a giant cutaneous squamous cell carcinoma in his right parotid region. Programmed radiotherapy had been previously terminated due to lesion ulceration and bleeding. He was characterized as a terminal case. We applied cemiplimab, which is an immune checkpoint inhibitor against the pro-grammed cell death receptor PD-1. After 6 months, the cutaneous squamous cell carcinoma had shrunk and had stopped bleeding. The patient was treated with methylprednisolone, cyclosporine, and mycophenolate mofetil during this period. He had 2 rejection episodes defined as doubling baseline serum creatinine with no other explanation. Both episodes were successfully treated with intravenous methylprednisolone, while immunotherapy was postponed for 10 days. In both cases, serum creatinine returned to baseline within 1 week. Immune checkpoint inhibitors are indicated for invasive cutaneous squamous cell carcinoma therapy, and the risk of acute rejection should not prevent the use of these agents in kidney transplant recipients, because immune checkpoint inhibitors may enhance the quantity and quality of life of such patients.

The Diabetes Eating Problem Survey-Revised (DEPS-R) in a Greek Adult Population with Type 1 Diabetes Mellitus: Model Comparison Supporting a Single Factor Structure.

Type 1 diabetes mellitus (T1DM) patients occasionally develop disordered eating behaviors, leading to insulin manipulation without medical consultation, targeting to achieve weight control. In clinical practice, the Diabetes Eating Problem Survey-Revised Version (DEPS-R) questionnaire has been used to evaluate eating disorders in T1DM patients. This study was conducted to validate the factor structure of the Greek version of DEPS-R using Confirmatory Factor Analysis (CFA), to investigate its reliability and convergent validity in Greek T1DM adults and to compare a single factor DEPS-R model with multiple factor models. Participants were 103 T1DM adults receiving insulin, who responded to DEPS-R. Their anthropometric, biochemical and clinical history data were evaluated. The sample presented good glycemic control and 30.1% scored above the established DEPS-R cut-off score for disturbed eating behavior. CFA results revealed that the data fit well to the factor models. The DEPS-R scale had good reliability and was positively linked to BMI, HbA1c, total daily dose and time in range. Model comparison supported the superiority of the 1-factor model, implying that Greek clinicians and practitioners might not have to consider individualized treatment based on various scores across different subscales but they can adopt a single DEPS-R score for an easy and efficient screening for disordered eating.

Small Extracellular Vesicles in Pre-Therapy Plasma Predict Clinical Outcome in Non-Small-Cell Lung Cancer Patients.

The potential use of plasma-derived small extracellular vesicles (sEV) as predictors of response to therapy and clinical outcome in chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) was explored. sEV were isolated by size-exclusion chromatography from the plasma of 79 chemotherapy-naïve NSCLC patients and 12 healthy donors (HD). sEV were characterized with regard to protein content, particle size, counts by qNano, morphology by transmission electron microscopy, and molecular profiles by Western blots. PD-1 and PD-L1 expression on circulating immune cells was analysed by flow cytometry. Pre-treatment levels of total sEV protein (TEP) were correlated with overall (OS) and progression-free survival (PFS). The sEV numbers and protein levels were significantly elevated in the plasma of NSCLC patients compared to HD (p = 0.009 and 0.0001, respectively). Baseline TEP levels were higher in patients who developed progressive disease compared to patients with stable disease (p = 0.007 and 0.001, stage III and IV, respectively). Patient-derived sEV were enriched in immunosuppressive proteins as compared to proteins carried by sEV from HD. TEP levels were positively correlated with CD8+PD-1+ and CD8+PD-L1+ circulating T cell percentages and were independently associated with poorer PFS (p < 0.00001) and OS (p < 0.00001). Pre-therapy sEV could be useful as non-invasive biomarkers of response to therapy and clinical outcome in NSCLC.

A Case of Cervical Carcinoid and Review of the Literature.

Uterine cervix carcinoids are distinct neuroendocrine cervical tumors, representing a comparatively small percentage of them. These well-differentiated neoplasms are far less prevalent than small- and large-cell carcinomas, characterized by a more favorable biological course. We report a case of a 43-year-old woman with a nonmetastatic cervical carcinoid, managed with radical hysterectomy. She still remains free of disease. Scant reports in the literature prohibit any reliable prediction of cervical carcinoid prognosis. Thus, prompt identification of the disease and subsequent therapeutic intervention could alter the final outcome.