American Association for Cancer Research
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Supplementary Figure 6 from Detection and Characterization of a Novel Subset of CD8+CD57+ T Cells in Metastatic Melanoma with an Incompletely Differentiated Phenotype

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journal contribution
posted on 2023-03-31, 16:52 authored by Richard C. Wu, Shujuan Liu, Jessica A. Chacon, Sheng Wu, Yufeng Li, Pariya Sukhumalchandra, James L. Murray, Jeffrey J. Molldrem, Patrick Hwu, Hanspeter Pircher, Gregory Lizée, Laszlo G. Radvanyi

PDF file - 89K, Accumulation of incompletely differentiated CD8+CD27+CD28+ effector-memory (TEM) lymphocytes co-expressing CD57 with high GB and low Perf expression in pleural effusions of metastatic breast cancer patients.



Purpose: Tumor‐specific T cells are frequently induced naturally in melanoma patients and infiltrate tumors. It is enigmatic why these patients fail to experience tumor regression. Given that CD8+ T cells mediate antigen‐specific killing of tumor cells, the focus of this study was to identify alterations in the differentiation of CD8+ residing at the tumor site, with emphasis on a population expressing CD57, a marker for terminal differentiation.Experimental Design: We conducted flow cytometric analysis of CD8+ tumor‐infiltrating lymphocytes (TIL) isolated from 44 resected melanoma metastases with known T‐cell differentiation markers. For comparison, peripheral blood mononuclear cells were isolated from matched melanoma patients. We sorted different CD8+ subsets found in TIL and determined their effector functions. In addition, we carried out Vβ clonotype expression analysis of T‐cell receptors to determine lineage relationship between the CD8+ TIL subsets.Results: The majority of CD8+ TIL was in the early-effector memory stage of differentiation. A significant population consisted of an oligoclonal subset of cells coexpressing CD27, CD28, CD57, and Granzyme B, with little or no perforin. These cells could be induced to proliferate, produce a high level of IFN-γ, and differentiate into CD27−CD57+, perforinhigh mature CTL in vitro. Addition of TGF‐β1 prevented further differentiation.Conclusions: Our studies identified a novel subset of incompletely differentiated CD8+ CTL coexpressing early effector memory and late CTL markers. This population resembles that found in patients with uncontrolled chronic viral infections. TGF-β1, frequently produced by melanoma tumors, may be a key cytokine inhibiting further maturation of this subset. Clin Cancer Res; 18(9); 2465–77. ©2012 AACR.