Abstract：
:Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1+ T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR+) T cells with an effector memory (TEM) profile are enriched in such lesions. Tumor-infiltrating lymphocytes coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently activated, nonexhausted phenotype. We also identified a subset of CD8+PD-1+FOXP3+ T lymphocytes at the earliest phase of functional differentiation after priming, termed "early effector cells" (EEC), which also exhibited an activated nonexhausted phenotype, but was less differentiated and associated with coexpression of multiple inhibitory receptors. In response to autologous tumor, EECs upregulated CD107a, produced IL2 and IFNγ, and were competent for differentiation. The identification of EECs marked by inhibitory receptor expression at tumor sites will enable investigations of early stages of adaptive antitumor immunity, as well as support the rationale for administering immunotherapy in early-stage non-small cell lung cancer. Cancer Res; 77(4); 851-61. ©2016 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Tassi E,Grazia G,Vegetti C,Bersani I,Bertolini G,Molla A,Baldassari P,Andriani F,Roz L,Sozzi G,Pastorino U,Mortarini R,Anichini Adoi
10.1158/0008-5472.CAN-16-1387subject
Has Abstractpub_date
2017-02-15 00:00:00pages
851-861issue
4eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-1387journal_volume
77pub_type
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