Assessment of the presence of interleukin 17+ macrophages and Th17 cells in situ in lip and oral tongue cancer.

Increasing clinical evidence indicates that Th17 cells may promote or inhibit tumor progression, however the exact role of these cells in Oral Squamous Cell Carcinoma (OSCCs) pathogenesis and progression remains unclear. Tumor associated macrophages are highly plastic phenotype cells which can differentiate as M1 or M2. The mechanism and cellular phenotype of IL-17 expressing macrophages are unknown. 40 cases of lip and 28 of tongue SCCs were submitted to immunohistochemical analysis, and histologically graded. In tongue cases TNM was analyzed. The number of IL-17+ T cells was higher in lip SCC (p = 0.028). IL-17+ macrophages was greater in tongue SCC (p = 0.014). There were more IL-17+ macrophages in the high-grade malignancy oral tongue SCCs (p = 0.016), yet there was no significant difference in the numbers of RORγt+ lymphocytes by histopathological or TNM analysis. This study provides evidence concerning IL-17's pleiotropic roles, being possibly dependent on its cellular sources in the tumor microenvironment.

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma.

The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

High CD3+ lymphocytes, low CD66b+ neutrophils, and scarce tumor budding in the invasive front of lip squamous cell carcinomas.

OBJECTIVE: This study aimed to evaluate tumor budding (TB) and quantify the neutrophilic and lymphocytic infiltration in the invasive front of lip squamous cell carcinomas. In addition, the associations between these features and the histopathological grading in the invasive front were analyzed. DESIGN: A total of 43 lip squamous cell carcinoma surgical specimens were included and classified in accordance with a histological invasive front grading system. Immunohistochemistry was performed for CD66b and CD3 for the evaluation of neutrophils and T lymphocytes, respectively, in the invasive front of the tumors. Tumor budding was evidenced by AE1/AE3 staining. RESULTS: Thirty-six (83.7%) of the tumors were well-differentiated tumors. Eleven (25.6%) of the cases exhibited high-intensity tumor budding. There were low neutrophil and high T lymphocyte infiltrations in the invasive front, leading to a low neutrophil/T lymphocyte ratio in the same region. Moreover, we found an association between tumor budding and the pattern of invasion, and between the CD3+ cell count and the inflammatory infiltrate (p < 0.05). CONCLUSIONS: The low neutrophil and high T lymphocyte infiltration in the invasive front, and the few high-intensity tumor budding cases are in accordance with the histopathological features of well-differentiated lip tumors. If these characteristics remain in lip squamous cell carcinomas with more aggressive histopathological features, it deserves to be investigated.

Immune response and evasion mechanisms in lip carcinogenesis: An immunohistochemical study.

OBJECTIVES: Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G) are considered immune checkpoint molecules that inhibit T-cell effectiveness, contributing to tumor immune escape. This study investigated PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip carcinogenesis. DESIGN AND RESULTS: Forty cases of lip squamous cell carcinoma (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC and AC, compared to HLM (p<0.05). PD-L1 was not associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCC, with AC exhibiting intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1+ and CD8+ cells (72.5%). PD-L1 was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was associated with lymph node metastasis in LSCC (p<0.05). CONCLUSIONS: PD-L1 and HLA-G-mediated immune evasion mechanisms are likely to occur from early pre-malignant to advanced malignant stages of lip carcinogenesis, which might provide a rationale for therapeutic blockade of these pathways. PD-L1 expression in LSCCs was correlated with the cytotoxic markers, suggesting that PD-L1 may appear as an escape mechanism in response to an active antitumor response.

Immunoexpression of human leukocyte antigen-DR in actinic cheilitis and lower lip squamous cell carcinoma

Abstract The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

CD8+ and FoxP3+ T-cell infiltration in actinic cheilitis.

BACKGROUND: Differences in immune profile between actinic cheilitis (AC), a precursor of lip squamous cell carcinoma, and normal lip vermillion (NL) have not been elucidated. OBJECTIVES: To compare density, distribution, and ratios of CD8+ and FoxP3+ cells between AC and NL and assess their associations with clinicopathologic variables. METHODS: Samples of AC and NL obtained between 2001 and 2013 at the College of Dentistry of the University of Concepcion, Chile, were retrospectively analyzed for immunohistochemical detection of CD8+ and FoxP3+ cells. Differences between groups were tested by Mann-Whitney U and Fisher's exact tests. Independent effects of cell densities and CD8/FoxP3 ratio with AC were assessed by multiple logistic regression analysis after adjustment for potential confounding. RESULTS: A total of 62 AC and 24 NL biopsies were included. Densities of CD8+ and FoxP3+ cells in AC were significantly higher than in NL. Conversely, the CD8+/FoxP3+ ratio was significantly lower in AC as compared to NL. After adjustment for sun exposure, age, gender, and smoking status, a stromal FoxP3+ cell density higher than 0.35 cells/field was significantly associated with increased odds of AC (odds ratio [OR] = 5.01, 95% confidence interval [CI]: 1.18-21.31), while a stromal CD8+/FoxP3+ ratio higher than 5.91 was associated with decreased odds of AC (OR = 0.29, 95% CI: 0.08-1.08). CONCLUSIONS: AC is characterized by increased FoxP3+ cell infiltration and a reduced CD8/FoxP3 ratio as compared to NL. Therefore, increased infiltration of FoxP3+ cells relative to CD8+ cells may contribute to the transition from normal to preneoplastic stages in lip carcinogenesis.

Immunoexpression of VEGFR-3, but not the immunoexpression of VEGF-C or lymphatic density, is correlated with metastasis in lower lip squamous cell carcinoma.

The purpose of this study was to evaluate the immunoexpression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3) and their correlation with intratumoural lymphatic density (ILD) and peritumoural lymphatic density (PLD) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty-five LLSCC with regional nodal metastasis and 25 LLSCC without metastasis were selected. The percentages of VEGF-C and VEGFR-3 staining in each tumour core and at the deep invasive front were assessed. PLD and ILD were determined using anti-podoplanin antibody. Immunohistochemical findings were correlated with nodal metastasis, clinical staging, local recurrence, clinical outcome, and histological grade. Cytoplasmic immunoexpression of VEGFR-3 in the tumour core was associated with metastasis (P=0.009), patient death (P=0.008), and histological grade (P<0.005). PLD, ILD, and VEGF-C expression showed no significant associations with clinicopathological parameters (P>0.05). PLD and ILD were not significantly correlated with the immunoexpression of VEGF-C or VEGFR-3 (P>0.05). There was a significant positive correlation between PLD and ILD (P=0.004), and between cytoplasmic immunoreactivity of VEGF-C and VEGFR-3 (P=0.011). These results suggest an important role for VEGFR-3 in the progression of LLSCC, and highlight the possible influence of its expression on the prognosis of these tumours. ILD and PLD may not be associated with lymph node metastasis in LLSCC.

Immunohistochemical expression of DNA methyltransferases 1, 3a, and 3b in actinic cheilitis and lip squamous cell carcinomas.

BACKGROUND: Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer. METHODS: Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b. RESULTS: Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05). CONCLUSIONS: The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer.

CD1a+ and CD83+ Langerhans cells are reduced in lower lip squamous cell carcinoma.

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant lesion diagnosed in the lip of patients chronically exposed to the sun that may give rise to a fully invasive lower lip squamous cell carcinoma (LLSCC). It is known that ultraviolet radiation causes dendritic cells (DCs) depletion in the epidermis, but the role of this cellular population in lip cancer progression remains uncertain. Therefore, this study investigated the distribution of DCs in normal, dysplastic and neoplastic tissues of the lower lip. METHODS: Thirteen cases of lower lip mucocele, 42 of ACs and 21 of LLSCC were retrieved and original diagnoses confirmed by two oral pathologists, who further classified ACs as low- and high-risk lesions. Immunoreactions against CD1a and CD83 identified immature and mature DCs, respectively. RESULTS: Immature CD1a+ Langerhans cells (LCs) were significantly decreased in LLSCC when compared to morphologically normal (P < 0.009) and dysplastic epitheliums (P < 0.003), whereas mature CD83+ LCs were significantly decreased in LLSCC when compared to normal epithelium (P = 0.038). There was no significant difference between low- and high-risk ACs regarding CD1a+ and CD83+ LCs (P > 0.05), but ACs demonstrated a lower concentration of CD1a+ LCs than normal epithelium (P < 0.009). There was no significant difference in the distribution of CD1a+ and CD83+ interstitial dendritic cells (IDCs) in the connective tissue among the studied groups (P > 0.05). CONCLUSION: These results suggest that depletion of epithelial LCs, but not IDCs in the connective tissue, would represent an important step for lip cancer development.

Regulatory T cells in the actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions. METHODS: The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects. RESULTS: The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-ß (TGF-ß), and low IFN-γ were detected in the potentially malignant lesions. CONCLUSION: Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment.

Imunoexpressão a il-17 e ror-yt em carcinomas de células escamosas de lábio e língua / Immunoreactivity to il-17 and ror-yt in squamous cell carcinomas of the lip and tongue

As células Th17 têm sido fortemente associadas à patogenia de doenças autoimunes e inflamatórias, porém sua influência na carcinogênese ainda é pouco conhecida, havendo relatos de suas ações tanto antitumorais quanto pró-tumorais. O objetivo do presente trabalho foi pesquisar a presença da linhagem Th17 intratumoral em CCE de lábio e língua, através da análise da imunoexpressão da IL-17 e do RORγt, relacionando estes achados com dados clínicos e morfológicos na tentativa de melhor compreender o papel dessas células na imunidade tumoral dos CCEOs. Na análise histomorfológica, observou-se predomínio de lesões de baixo grau em lábio e de alto grau em língua (p = 0,024). Não foi observada significância estatística entre estadiamento clínico e gradação histológica de malignidade (p = 0,644). Para o estudo imunoistoquímico, 5 campos aleatórios com maior imunorreatividade do infiltrado inflamatório peritumoral foram fotomicrografados no aumento de 400x. Realizou-se a contagem de linfócitos que exibiram marcação citoplasmática e pericitoplasmática para a citocina IL-17 bem como nuclear e citoplasmática para o RORγt. Foi observada diferença estatisticamente significativa na quantidade de linfócitos imunopositivos para IL-17 entre os grupos de CCE de lábio e língua (p = 0,028). Para o RORγt não foi observada diferença estatisticamente significativa entre os grupos de CCE de lábio e língua (p = 0,915). Não foi observada diferença estatística entre a imunomarcação da IL-17 e RORγt com gradação histológica de malignidade e com estadiamento clínico. Os achados dessa pesquisa sugerem um possível papel antitumoral da IL-17 para os casos de lábio. Os resultados da análise do RORγt, possivelmente se devem à ampla dualidade do papel pró-tumoral e antitumoral das células Th17 e à sua plasticidade que, na presença de diferentes citocinas expressas no microambiente tumoral, podem alterar seu fenótipo. (AU)

Th17 cells have been strongly associated to the pathogenesis of inflammatory and autoimmune diseases, although their influence on the carcinogenesis is still little known, there are reports of anti-tumor and protumoral actions. The objective of this study is to research the presence of Th17 lineage in lip and tongue SCC, using the analysis of the immunoexpression of IL-17 and RORγt, relating this immunoexpression with clinical and morphological findings in the attempt to better comprehend the role of these cells on the tumoral immunity of OSCCs. The results were submitted to non-parametric statistical tests with significance level of 5%. On the histomorphological analysis, it was observed the predominance of low level lesions on lip and high level lesions on tongue (p=0,024). It was not observed statistical significance between clinical stage and histological gradation of malignancy (p=0,644). For the immunohistochemical study, 5 random fields with greater immunoreactivity of the peritumoral inflammatory infiltrate were photomicrographed on the 400x magnification. It was done the count of lymphocytes which showed cytoplasmic and pericytoplasmic staining for the IL-17 cytokine as well as nuclear and cytoplasmic staining for RORγt. It was observed statistical significance difference on the quantity of immunopositive lymphocytes to IL-17 between the groups of SCC of lip and tongue (p=0,028). For the RORγt it was not observed statistical significance difference between the groups of SCC of lip and tongue (p=0,915). It was not observed statistical difference between the immunostaining of IL-17 and RORγt with histological gradation of malignancy and clinical staging. The findings of this research suggest a possible anti-tumor role of IL-17 for cases of lip. The results of the analysis of the RORγt are possibly due to the wide duality of the anti-tumor and protumoral role of the Th17 cells and their plasticity which, in the presence of different cytokines expressed on the tumor microenvironment, can alter its phenotype. (AU)

Regulatory T cells in the actinic cheilitis

BACKGROUND: Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions. METHODS: The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects. RESULTS: The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-ß (TGF-ß), and low IFN-γ were detected in the potentially malignant lesions. CONCLUSION: Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment.

Keratoacanthoma in the inferior lip of an immunosuppressed patient. A case report.

Keratoacanthoma is a lesion typical crater, symmetrical, rounded, rapid growth with high potential for self-involution. The lesions may be multiple, disseminated and associated with some syndromes. The etiology of keratoacanthoma is not known, but it is often observed in patients chronically exposed to sun. Histopathological features of keratoacanthoma may resemble those of a well differentiated squamous cell carcinoma. The hallmark of the disease is spontaneous resolution after an intermediary stationary stage. The majority of the cases is treated by surgical excision. For this reason, very few cases have been documented until resolution, which constitutes the gold standard for this clinic diagnosis. The aim of this article is to report a case of keratoacanthoma in the inferior lip of an immunosuppressed patient.

Distinct expression of perforin and granzyme B in lip and oral cavity squamous cell carcinoma.

BACKGROUND: Perforin and granzyme B (GB) are the main constituents of cytotoxic T-lymphocyte granules, and they have important roles in preventing the initiation and progression of cancer. METHODS: The aim of this study was to compare the expression of CD8(+) /perforin(+) double-staining and GB(+) cells, by immunohistochemistry, in primary oral cavity squamous cell carcinoma (OCSCC), lip squamous cell carcinoma (LSCC), non-dysplastic leukoplakia (LK), dysplastic LK, actinic cheilitis (AC), oral lichen planus (LP) and normal oral mucosa. RESULTS: Our results showed a higher expression of CD8(+) /perforin(+) and GB(+) cells in LSCC when compared with the samples of OCSCC, non-dysplastic and dysplastic LK, AC, oral LP and normal oral mucosa. In addition, increased CD8(+) /perforin(+) and GB(+) cell numbers were observed in all pre-malignant lesions (non-dysplastic LK, dysplastic LK, AC) when compared with the control. CONCLUSIONS: Perforin and GB proteins may contribute to antitumoural immunity, leading to the direct killing of tumour cells; however, it seems to occur more effectively in LSCC than OCSCC.

Lip cancer in renal transplant patients.

The aims of this study were to establish the incidence of lip cancer (LC) in a population of renal transplant patients (RTPs), identifying possible risk factors and predictable variables, and to describe the clinical appearance, treatment, and course of LC in this group. The study included 500 patients (307 men, 193 women; mean age 53.63±13.42 years, range 19-95 years; mean period since transplant 59.66±55.81 months, range 4-330 months). Incident cases of LC were ascertained retrospectively from outpatient records. All LC lesions were sampled by biopsy and examined histopathologically. Six of the men (1.2%) suffered lower LC, and LC cases showed significant differences on univariate analysis for tobacco habit, tobacco consumption, and sun exposure. All patients who had LC were taking prednisolone and cyclosporine A (CsA) at the time of LC diagnosis. The median interval for LC incidence after renal transplant was 80.50±31.25 months. Five of six LCs were squamous cell carcinomas. Multiple logistic regression showed that the LCs were not significantly associated with any independent risk factor. The results show that the appearance of LC in RTPs is associated with immunosuppressant treatment, sun exposure, and tobacco and indicate that these patients should avoid unprotected exposure to sunlight and smoking. Because of the high incidence of LC in RTPs, periodic checking of the lips is important to ensure prompt diagnosis and correct management of LC. Our data suggest that the clinical profile of LC in this patient group is similar to that of the general population.

Analysis of local immunity in squamous cell carcinoma of the tongue and lower lip.

Antitumor immunity plays an important role in the development of and protection against malignancy. In general, patients with cancer are known to be immunologically compromised. The objective of this study was to evaluate local immunity in squamous cell carcinomas (SCCs) of the tongue and lower lip by immunohistochemistry, using anti-CD3, -CD4, -CD8, -CD25 and -zeta antibodies. Immunoexpression at the invasive front was compared considering anatomical tumor location and metastasis. The CD4/CD8 ratio was calculated for each case and associated with the variables. CD3+, CD4+, CD8+ and CD25+ cell counts were higher in SCCs of the lower lip and anti-zeta immunostaining was more evident in non-metastatic cases. CD8+ and CD25+ cell counts were also significantly correlated with tumor location (p=0.004 and p=0.004, respectively), with the observation of a larger number of these cells in SCCs of the lower lip. The CD4/CD8 ratio showed no significant association with metastasis or anatomical location. In conclusion, the clinical behavior of the oral SCC cases studied might be partially related to the immunohistochemical profile of the inflammatory infiltrate present at the invasive front.

Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND: CD8+ and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival. METHODS: The aim of this study was to evaluate the population of CD8+ and NK cells, by immunohistochemistry, in samples of oral cavity squamous cell carcinoma (OCSCC) and lip squamous cell carcinoma (LSCC), leukoplakia, actinic cheilitis, and healthy oral mucosa (control). The relationship of CD8+ and NK cells with survival data, lymph node metastasis, tumor size, and proliferative index was also evaluated. RESULTS: The number of peritumoral and intratumoral CD8+ and NK cells was significantly higher in LSCC, when compared with control, pre-malignant lesions, and OCSCC. A higher proportion of peritumoral CD8+ cells demonstrated correlation with a lower neoplastic proliferative index. Moreover, patients with OCSCC with a high density of peritumoral CD8+ cells showed a tendency towards a longer survival time. CONCLUSIONS: The differential CD8+ and NK cells infiltration in oral SCC might reflect a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.

Squamous cell carcinoma of the lower lip: FAS/FASL expression, lymphocyte subtypes and outcome.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clincopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (P<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.

[Effects of thermochemotherapy on immunologic function of patients with lip cancer].

OBJECTIVE: To evaluate the effects of thermochemotherapy on the immunologic function of lip cancer patients and to provide a theoretical basis for the clinical application of thermochemotherapy. METHODS: Twenty patients were heated by microwave at (42.5 +/- 0.2) degree C for 40 minutes after venoclysis of Pingyangmycin (8 mg) and Methotrexate (20 mg). Each of the patients received the therapy twice a week for 5 weeks. Venous blood was obtained before the first thermochemotherapy and after the tenth thermochemotherapy. Lymphocyte transformation index was examined by 3H-TdR method, and CD4+ and CD8+ T cells were assayed by flow cytometry. RESULTS: The tumors of the 20 patients were completely extinctive. The lymphocyte transformation index after treatment was significantly higher than that before treatment (P < 0.01). The CD4+ T cells and CD4+/CD8+ after treatment were significantly higher than those before treatment (P < 0.05); the CD8+ T cells after treatment was lower than that before treatment, but there was no statistically significant difference (P > 0.05). CONCLUSION: Thermochemotherapy can enhance the lip cancer patient's T lymphocyte immunologic function, which possibly plays an important role in the treatment of lip cancer.