Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence le rôle, dans la réponse des cellules cancéreuses aux immunothérapies adoptives, des lymphocytes T CD8+ ayant des propriétés similaires à celles des cellules souches hématopoïétiques
Adoptive cell transfer (ACT) is a type of immunotherapy that uses a patient's own T lymphocytes to recognize and attack cancer. ACT has been effective in treating certain patients with metastatic melanoma and is being applied to treat some epithelial cancers. Krishna et al. investigated why some cancer patients respond to ACT, whereas others do not. They identified a population of CD8+ T cells that had stem-like surface markers that were associated with effective tumor cell killing and favorable response of melanoma patients to ACT. Only a small subset of T cells specific against tumor mutations were found in this stem-like state, whereas most mutation-reactive T cells were terminally differentiated. These findings could be of value in improving cancer immunotherapy outcomes.Science, this issue p. 1328Adoptive 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.
Science 2020