Activated status of tumour‐infiltrating lymphocytes and apoptosis in testicular seminoma

Abstract

Testicular seminoma is characterized by a prominent lymphoid infiltrate and an excellent prognosis. Cytotoxic T-lymphocytes (CTLs) infiltrating seminoma tumour nests constitute a major subset of the lymphoid infiltrate. The objective of this study was to determine whether CTLs express markers of cytotoxic potential and activity and whether the number of activated CTLs correlates with the extent of apoptosis in testicular seminomas, as opposed to non-seminomatous testicular germ cell tumours (NSTGCTs). Twenty cases of pure seminoma as well as 20 cases of NSTGCTs including 16 mixed germ cell tumours (MGCTs) were studied. Immunohistochemistry for the cytotoxic markers TIA-1 (cytotoxic potential) and granzyme B (cytotoxic activity) and the T-cell markers CD3 and CD8 was performed on formalin-fixed, paraffin-embedded sections. The apoptotic index (AI) was determined by the TUNEL method. The number of CD3(+), CD8(+), TIA-1(+), and granzyme B(+) cells in tumour cell nests was markedly increased in testicular seminomas, compared with NSTGCTs (p<0.01). Activated granzyme B(+) cells numbered 25.6+/-5.2 per high power field in seminomas and 8.9+/-3.2, 8.1+/-3.9, and 0.4+/-0.2 for embryonal carcinomas, yolk sac tumours, and immature teratomas, respectively. Double immunohistochemical staining for granzyme B and CD8 revealed that 82.6+/-8.5% of granzyme B-expressing cells were CD8(+). The tumour cell AI was significantly increased in embryonal carcinoma, compared with the seminoma, yolk sac tumour, and immature teratoma subgroups (6.7+/-1.3, 2.3+/-0.3, 3.0+/-1.1, and 2.3+/-1.1, respectively, p<0.001). TUNEL/CD3 double immunostaining revealed that a significant proportion of the apoptotic seminomatous tumour cells were in direct contact with one or more CD3(+) lymphocytes (47.2+/-6.2%). The number of activated granzyme B(+) CTLs showed a strong linear correlation with the AI in the seminoma group (r=0.71, p<0.0001) but not in other subgroups. TUNEL/granzyme B double immunolabelling revealed that a proportion of activated granzyme B(+) lymphocytes (20%) were often seen in close contact with apoptotic tumour cells. The presence of increased numbers of activated cytotoxic lymphocytes in testicular seminomas suggests that apoptotic tumour cell death in this neoplasm may be triggered by cytotoxic granule effectors. This phenomenon may be one of the key host immune mechanisms leading to the excellent prognosis in this tumour.

Risk of Germ Cell Tumors among Men with HIV/Acquired Immunodeficiency Syndrome

“…Tumor-infiltrating lymphocytes correlate directly with better seminoma prognosis (4,7,24,25). For men with HIV/AIDS, we found that seminoma risk was significantly higher for disseminated than for earlier stages.…”

Lymphocyte recruitment into the tumor site is altered in patients with MSI-H colon cancer

“…The infiltration of a tumor with various immune cells has been correlated with increased host survival and decreased metastases of the cancer in some instances [12][13][14][15][16] although this is not the case for all cancers [17,18]. Studies have demonstrated that high levels of tumor infiltrating lymphocytes (TILs) are a feature associated with MSI-H colorectal cancer [19,20].…”

“…The role of the immune response in controlling metastatic events has been well-described [12][13][14][15]. The infiltration of a tumor with various immune cells has been correlated with increased host survival and decreased metastases of the cancer in some instances [12][13][14][15][16] although this is not the case for all cancers [17,18].…”

Intratumoral CD8+ T Lymphocytes as a Prognostic Factor of Survival in Endometrial Carcinoma

“…Natural killer cells are virtually absent in endometrial tumors (11). Activated CTLs expressing TIA-1 and/or granzyme B cytotoxic granules have been demonstrated in certain human neoplasms, such as EBV-associated gastric cancer, medullary carcinoma of the breast, germ cell tumors of the testis, and carcinomas of the colon, cervix, esophagus, and kidney (12)(13)(14)(15)(16)(17)(18).…”