Journal
SCIENCE
Volume 370, Issue 6522, Pages 1328-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abb9847
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Funding
- Center for Cancer Research intramural research program of the National Cancer Institute
- NCI Director's Innovation Award
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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.
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