Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

Adoptive T cell therapy (ACT) using ex vivo–expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39–CD69–) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39+ state. However, ACT responders retained a pool of CD39– stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.

Source: ScienceNOW - December 10, 2020 Category: Science Authors: Krishna, S., Lowery, F. J., Copeland, A. R., Bahadiroglu, E., Mukherjee, R., Jia, L., Anibal, J. T., Sachs, A., Adebola, S. O., Gurusamy, D., Yu, Z., Hill, V., Gartner, J. J., Li, Y. F., Parkhurst, M., Paria, B., Kvistborg, P., Kelly, M. C., Goff, S. L., Tags: Immunology, Medicine, Diseases reports Source Type: news