T Effector T Cell Immune Responses in Cancer

Several authors have identified percentage, phenotype, and function of T cells in ageing cancer patients both pre and post treatment with the aim to use these immunologic markers as prognostic for patient outcome. Tumor-infiltrating lymphocytes seem to play an important role in anti-cancer immunity. Ebelt et al. [82] found in prostate cancer that T lymphocytes (mainly CD4+ T cells) form a cluster outside the carcinoma-infiltrating tissue in 17 non-treated patients (59-78 years old). However, almost no effector function was detected as IFN-gamma and perforin were down- regulated on infiltrating lymphocytes compared to cells of healthy prostate tissue suggesting that infiltrating T cells with subverted function could be present at the tumor site and contribute for cancer development.

Ramirez et al. [83] evaluated patients with resected stage IIB-IV melanoma (1587 years old) submitted to vaccination (12MP, multipotent vaccine derived from melanocytic differentiation antigens and cancer testis antigens) and verified the immune response (IR) based on ELIspot (interferon-gamma) from the peripheral blood mononuclear cells and increase on the CD8+ T cells. The 7 week cumulative incidence rate of IR was 53 % (130/249) in patients <64 years old and 38 % (30/78) in older patients over 64. Gender had no impact on IR and was not related with clinical outcome but there was a trend toward improved survival in males. The authors noted that even though patients older than 64 years old were able to mount an IR after vaccination, had 5 years disease free survival and overall survival not statistically different from patients under 64 years, their results may not apply to frail older adults as only patients with good functional status were included in the study.

Saavedra et al. [84] evaluated patients with stage IIIB or IV non-small cell lung cancer (NSCLC); 30 had not started first-line chemotherapy and 36 were treated with platinum-based chemotherapy. They received an EGF vaccine designed to induce specific antibodies against the epidermal growth factor (EGF) and had the percentage of T and B cells measured. CD4+, CD 8+ and B cells were diminished in cancer patients regardless of chemotherapy in addition to the significant decrease in CD4/CD8 ratio. Terminally differentiated T cells (CD4+CD45RA+28- and CD8+CD45RA+CD28-) were not different when cancer patients and healthy individuals were compared. Vaccinated patients with high CD4+ T cells and CD4/CD8 ratio and low CD8+CD28- frequency as baseline values achieved a higher median survival suggesting that immu- nosenescence markers could provide support for determining whether patients could benefit from immunotherapy and be predictive of vaccine efficacy. In hepatocellular carcinoma patients (58-81 years old), a lower percentage of WTp5 3264-272-specific naive (CD45RA+) and higher percentages of WTp53149-157 and WTp5 3264-272-specific memory (CD45RO+) CD8+ T cells were observed and confirmed by CTL reactivity detection (granzyme B, IFN-gamma) suggesting interactions between the developing tumor and the host immune system [85].

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