Immunohistological characterisation of tumor infiltrating lymphocytes (TIL) in malignant melanoma and the evaluation of regulatory T cells in tumor tissue and circulation for the assessment of its relationship with prognosis

The immunotherapists have begun to focus on malignant melanoma, in which unlike most other solid tumors, spontaneous regression can be seen due to the specific immune response. Thus in nowadays, it has been listed among the successful goals of immunotherapeutic approaches. In order to clarify the role of regulatory T cells (Treg) in melanoma, further detailed studies should be performed. The main objective of this study is the immunohistological characterization of tumor infiltrating lymphocytes and to determine the prognostic efficacy of Treg cells in circulation by comparing serum S100B levels. Therefore, the analysis of phenotype and quantity of Treg?s are performed in both melanoma patients (n=30) and healthy controls (n=24) by using the most suitable Treg marker FOXP3 transcription factor. Additionally, TILs are immunohistochemically evaluated.In this study, higher serum levels of S100B and CD4+CD25+, CD4+CD25+FOXP3+, and CD8+CD25+FOXP3+ cells are obtained in the patient group comparing to control group. Negative correlation is found between serum S100B and CD4+ cells and tumor infiltrating B lymphocytes in peripheral blood circulation. It was shown that tumor infiltrating T lymphocyte numbers were decreased when the Breslow thickness was increased. It was also seen that tumor infiltrating CD4+ lymphocyte numbers were decreased when the Clark level was increased.According to our results, there was a correlation between the tumor progression and the clinical status of the patients and the measurement of serum S100B and Treg?s in blood circulation. Moreover, it is possible to say that, there is a negative correlation between the prognosis and presence of TIL?s. The lower quantity of lymphocytes which should suppress the tumor is responsible for tumor development.The final data of this study suggest a possible role of Treg?s in anti-tumor immunity. For future it can be said that it is useful to design studies to investigate Treg?s in terms of specific marker expression, inhibition mechanism, and antigen specificity. Thus, novel cancer vaccine formulations, aiming to favor the expansion of CD4+ T cells, and to limit Treg cell expansion, should be evaluated in conjunction with CD8+ T cells and at the level of antigen specific immune responses.