The predictive value of CD8, CD4, CD68, and human leukocyte antigen‐D‐related cells in the prognosis of cutaneous malignant melanoma with vertical growth phase

Abstract

BACKGROUND. To establish the prognostic value of immune system cells that infiltrate melanoma, the authors evaluated the distribution and density of T lymphocyte subsets, macrophages, and dendritic cells in samples of primary cutaneous melanoma from 47 patients with Stage I and II melanoma according to the American Joint Committee on Cancer staging system. \ud \ud METHODS. immunohistochemical demonstrations of CD8 and CD4 lymphocytes, CD68 macrophages, human leukocyte antigen-D-related (HLA-DR) cells, S-100 protein, and melanoma-associated antigens Melan A and HMB-45 were performed. The results were derived from independent histopathologic reviews by two pathologists. The low-density, moderate-density, and high-density groups of cells that infiltrated the base of the tumor during the vertical growth phase were compared with the overall survival rate using the Kaplan-Meier method and the log-rank test. Clinical variables (gender, age, tumor location, Clark level, vascular/lymphatic invasion, and thickness) also were analyzed. \ud \ud RESULTS. The CD8 lymphocytes exhibited independent statistically positive significance in survival (log-rank test, 8.49; P = 0.01) between patients in different lymphocyte density groups. There was a difference in 5-year survival among patients in the high-density group (78.8%), the moderate-density group (44.4%), and the low-density group (25.0%). The CD4 lymphocytes, which were less numerous than CD8 cells, had similar distribution. There also was a correlation of HLA-DR cells with overall survival (log-rank test, 5.29; P = 0.02). CD68 cell density was not found to be correlated with survival. \ud \ud CONCLUSIONS. The presence and number of infiltrating CD8 lymphocytes as well as the overall occurrence of HLA-DR cells may be considered independent, favorable prognostic factors in melanoma. The current results may be important for identifying other prognostic factors with which to evaluate disease progression and develop immune therapies for patients with melanoma

Inflammatory monocytes are potent antitumor effectors controlled by regulatory CD4+T cells

“…Tregs may, thus, not be the main suppressor cells at the tumor site, whereas other suppressive cells may hamper antitumor immunity locally in our model. In line with such an assumption, we have recently shown that type 2 macrophages infiltrate massively the most aggressive metastases (21), which is consistent with observations in human melanoma biopsies (26)(27)(28). In contrast, the proportion of Tregs among CD4 + T cells was increased in the spleen and TdLNs of MT/ret mice without vitiligo, in agreement with the accumulation of Tregs observed in TdLNs few days after tumor cell implantation in several transplanted tumor models (7).…”

IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells

“…Conversely, CD8 + T lymphocytes are potent effectors of adaptive tumor immunity through their production of IFN-γ as well as initiation of perforin/granzyme or Fas ligand-dependent cytolysis following TCRmediated engagement by tumor antigens (3,4). The presence of CD8 + T cells in ovarian, colorectal, and melanoma patient tumors is correlated with improved survival and can be a better prognostic indicator than conventional tumor staging (5)(6)(7).…”

Association of microvessel density with infiltrating cells in human cutaneous malignant melanoma

“…14,33,62 Unlike in other tumor types, 24,33,37,41 a prognostic role of macrophage infiltration was not confirmed in cutaneous melanoma. 50 Beside macrophages, T lymphocytes are often major components of tumor infiltrates in many solid tumors, and their central role in antitumor immunity is well established. However, tumor-infiltrating T cells have been shown to be functionally defective, incompletely activated or anergic.…”