The Association of CD8+ Cytotoxic T Cells and Granzyme B+ Lymphocytes with Immunosuppressive Factors, Tumor Stage and Prognosis in Cutaneous Melanoma

被引:4
作者
Salmi, Satu [1 ]
Halinen, Kaisla [1 ]
Lin, Anton [1 ]
Suikkanen, Sanna [2 ]
Jokelainen, Otto [2 ,3 ]
Rahunen, Eija [1 ]
Siiskonen, Hanna [2 ]
Pasonen-Seppanen, Sanna [1 ]
机构
[1] Univ Eastern Finland, Inst Biomed, Kuopio 70211, Finland
[2] Kuopio Univ Hosp, Dept Clin Pathol, Kuopio 70029, Finland
[3] Univ Eastern Finland, Inst Clin Med, Clin Pathol, Kuopio 70029, Finland
基金
芬兰科学院;
关键词
melanoma; tumor microenvironment; lymphocytes; immunosuppression; PD-L1; EXPRESSION; IMMUNE; RESPONSES;
D O I
10.3390/biomedicines10123209
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The immunosuppressive tumor microenvironment (TME) consists of suppressive cells producing a variety of immunomodulatory proteins, such as programmed death ligand 1 (PD-L1) and indoleamine-2,3-dioxygenase (IDO). Although granzyme B (GrB) is known to convey the cytolytic activities of CD8+ cytotoxic lymphocytes, it is also expressed by other cells, such as regulatory T and B cells, for immunosuppressive purposes. The role of GrB+ lymphocytes in melanoma has not been examined extensively. In this study, benign, premalignant, and malignant melanocytic tumors were stained immunohistochemically for CD8 and GrB. PD-L1 was also stained from malignant samples that had accompanying clinicopathological data. The association of CD8+ and GrB+ lymphocytes with PD-L1 expression, tumor stage, prognosis, and previously analyzed immunosuppressive factors were evaluated. Our aim was to obtain a more comprehensive perception of the immunosuppressive TME in melanoma. The results show that both CD8+ and GrB+ lymphocytes were more abundant in pT4 compared to pT1 melanomas, and in lymph node metastases compared to primary melanomas. Surprisingly, a low GrB/CD8 ratio was associated with better recurrence-free survival in primary melanomas, which indicates that GrB+ lymphocytes might represent activated immunosuppressive lymphocytes rather than cytotoxic T cells. In the present study, CD8+ lymphocytes associated positively with both tumor and stromal immune cell PD-L1 and IDO expression. In addition, PD-L1+ tumor and stromal immune cells associated positively with IDO+ stromal immune and melanoma cells. The data suggest that IDO and PD-L1 seem to be key immunosuppressive factors in CD8+ lymphocyte-predominant tumors in CM.
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页数:15
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