Implication of chemo-resistant memory T cells for immune surveillance in patients with sarcoma receiving chemotherapy

Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8⁺ memory T cell population with a chemo-resistance property, "young memory" T (T_YM ) cells. In this study, we investigated the proportion and function of T_YM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of T_YM cells was significantly decreased in patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only T_YM cells but also T_CM and T_EM cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from T_YM , T_CM and T_EM cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from T_YM cells but were hardly induced from T_EM cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from T_YM cells but not from the T_CM and T_EM cells in sarcoma patients who received chemotherapy. The findings suggest that T_YM cells are resistant to chemotherapy and can firstly recover from the nadir. T_YM cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy.