Marked anti-tumor effects of CD8⁺CD62L⁺T cells from melanoma-bearing mice

Abstract

CD8(+)CD62L(+) T cells have been shown to play pivotal roles in anti-viral immunity, chronic myeloid leukemia and renal cell carcinoma. Recently, CD8(+)CD62L(+) T cells from naïve mice (nCD8(+)CD62L(+) T cells) have shown superior anti-tumor properties in melanoma-bearing mice. Considering that antigen-specific memory T cells have shown to possess more potent immunity than non-specific memory T cells, we hypothesized that CD8(+)CD62L(+) T cells from tumor-bearing individuals (mCD8(+)CD62L(+) T cells) might have superior anti-tumor effect than nCD8(+)CD62L(+) T cells. Therefore, we investigated phenotypes, functions and the in vivo distribution of mCD8(+)CD62L(+) T cells in tumor-bearing mice. We found that, while keeping the features of central memory T cells, the frequency of mCD8(+)CD62L(+) T cell in the spleen of tumor-bearing mice was significantly higher than that the one of nCD8(+)CD62L(+) T cell in naive mice. Moreover, we demonstrated that mCD8(+)CD62L(+) T cells had higher proliferation rate and IFN-γ production than nCD8(+)CD62L(+) T cells, in vitro. We performed adoptive transfer of mCD8(+)CD62L(+) T cells into melanoma-bearing mice and tracked them in spleen, lymph nodes and in melanoma tissues. Our results show that mCD8(+)CD62L(+) T cells had stronger in vivo anti-tumoral activity than nCD8(+)CD62L(+) T cells. This study highlights the therapeutic potential of mCD8(+)CD62L(+) T cells in the immunotherapy of melanoma and possibly other tumors.

Differential Cytokine Utilization and Tissue Tropism Results in Distinct Repopulation Kinetics of Naïve vs. Memory T Cells in Mice

“…In addition to these, it is also proposed that the lymphoid homing molecule L-selectin (CD62L), which is usually associated with a naïve phenotype promotes anti-tumor effects in ACT. Such propensity is illustrated in the superior effector function of naive T cells and central memory T cells both of which are marked by the expression of CD62L (62). On the other hand, there are also conflicting data about the role of CD62L in ACT (63), where the failure to express CD62L did not impair the function of donor T cells and did not alter the outcome of T cell adoptive immunotherapy in mice (63).…”

T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy

“…Thus, diverse T cell subsets over a range of differentiation states may be optimal, as both speculated and evidenced by findings that CD8 + T em and T eff cooperativity were needed for long-term tumor control in responding melanoma patients and that CD8 + T cm showed better anti-melanoma activity than did naïve T cells. 176,271 Accessory help provided by tumor-specific CD4 + lymphocytes is another consideration based on their noted presence in at least 20% of metastatic melanomas and well-recognized roles in orchestration of immune anti-tumor activities. 272 Finally, choice of CD8 + Tc and CD4 + Th type and respective ratios will also factor heavily in ACT bolus preparations.…”

Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma

“…Naïve CD8 + cells and central memory CD4 + and CD8 + cells showed higher values in RCC patients. Central memory T cells play an important role in tumor antigen recognition and tumor control, which could be an explanation for their higher counts in RCC patients [ 16 , 17 ]. In the majority of lymphocyte subsets, especially in activated and memory CD4 + cells as well as different types of activated and memory CD8 + cells, significantly lower values were observed in RCC patients independently of age or gender.…”