Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L

CD62L governs the circulation of CD8⁺ T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8⁺ T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8⁺ T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8⁺ cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L^−/− CD8⁺ T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L^−/− CD8⁺ T cells were functionally indistinguishable from CD62L^+/+ CD8⁺ T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8⁺ T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT^−/− animals), CD8⁺ T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8⁺ T cells.