期刊
CANCER IMMUNOLOGY RESEARCH
卷 5, 期 5, 页码 408-416出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-16-0333
关键词
-
资金
- NIH [R01 DE019727, P50 CA097190, CA206517]
- University of Pittsburgh Cancer Institute [P30CA047904]
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8(+) tumor-infiltrating lymphocytes (TIL) and compared them with those of peripheral blood T lymphocytes (PBL) in patients with head and neck cancer (HNSCC) during cetuximab therapy. The frequency of PD-1 and TIM-3 expression was significantly increased in CD8(+) TILs compared with CD8(+) PBLs (P = 0.008 and P = 0.02, respectively). This increased CD8(+) TIL population coexpressed granzyme B/perforin and PD-1/TIM-3, which suggests a regulatory role for these immune checkpoint receptors in cetuximab-promoting cytolytic activities of CD8(+) TILs. Indeed, the increased frequency of PD-1(+) and TIM-3(+) CD8(+) TILs was inversely correlated with clinical outcome of cetuximab therapy. These findings support the use of PD-1 and TIM-3 as biomarkers to reflect immune status of CD8(+) T cells in the tumor microenvironment during cetuximab therapy. Blockade of these immune checkpoint receptors might enhance cetuximab-based cancer immunotherapy to reverse CD8(+) TIL dysfunction, thus potentially improving clinical outcomes of HNSCC patients. (C) 2017 AACR.
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