CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3+ regulatory T cells with respect to lethal prostate cancer

Abstract

Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T regs ), a subpopulation of T cells that have a role in promoting tumor growth. T regs counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n ¼ 261) and controls are men who survived 410 years after their diagnosis (n ¼ 474). Infiltration of both T helper and T cytotoxic cells was frequently observed and the majority of the T regs were CD4 þ . T helper or T cytotoxic cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4 þ T reg cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4 þ T regs in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4 þ T regs in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

“…They did not, however, investigate how the different subsets of T lymphocytes contributed to the clinical outcome. Ness et al showed that the negative prognostic effect may be mediated primarily through CD8 + lymphocytes rather than the overall density of T lymphocytes as measured by CD3 positivity [283], while Davidsson et al attributed the poor prognostic effect to T regs in the prostate cancer microenvironment [284]. Others have reported a correlation between FOXP3 + TILs in prostate cancer and biochemical recurrence [285], though Vesalainen et al reported that tumors with dense TILs were associated with higher survival rates than tumors with absent or decreased TILs [286].…”

Inflammation and prostate cancer: friends or foe?

“…Although conflicting results have been highlighted when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer, Davidsson et al [73] performed a case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Although infiltration of both CD4 ?…”

Remarkable Pathologic Change in Advanced Prostate Cancer Patient Using Dendritic Cell–Cytokine-Induced Killer Combined Therapy: A Case Report

“…17 One study compared the infiltration of both T helper and T cytotoxic cells between men who died of prostate cancer and those who survived for 10 years with prostate cancer. 18 Their results suggested that patients with increased numbers of CD4 þ Tregs in their prostate tumor environment had an increased risk of dying from prostate cancer. Since the approval of the dendritic-based cancer vaccine sipuleucel-T (Provenge) by the FDA in 2010, 19 an increasing number of immunotherapeutic agents are being tested in clinical trials for CRPC.…”

“…18 Their results suggested that patients with increased numbers of CD4 þ Tregs in their prostate tumor environment had an increased risk of dying from prostate cancer. Since the approval of the dendritic-based cancer vaccine sipuleucel-T (Provenge) by the FDA in 2010, 19 an increasing number of immunotherapeutic agents are being tested in clinical trials for CRPC. The aim of cancer immunotherapy is to overcome the weak immunogenicity of tumorassociated antigenic material and to provoke a robust immune response to cancer cells.…”