American Association for Cancer Research

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Supplemental Figure 2 from Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile

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posted on 2023-04-03, 23:26 authored by Christiane Querfeld, Samantha Leung, Patricia L. Myskowski, Shane A. Curran, Debra A. Goldman, Glenn Heller, Xiwei Wu, Sung Hee Kil, Sneh Sharma, Kathleen J. Finn, Steven Horwitz, Alison Moskowitz, Babak Mehrara, Steven T. Rosen, Allan C. Halpern, James W. Young

Sections show morphologic and immunohistochemical findings of MF lesion






Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T cells in a background of chronic inflammation. Although dendritic cells (DCs) stimulate T cells and are present in skin, cutaneous T cells in CTCL do not respond with effective antitumor immunity. We evaluated primary T-cell and DC émigrés from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5). Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3. CD8+ CTCL populations contained more T cells expressing CTLA-4 and LAG-3. CTCL populations also contained more T cells expressing the inducible T-cell costimulator (ICOS), a marker of T-cell activation. DC émigrés from healthy or CTCL skin biopsies expressed PD-L1, indicating that maturation during migration resulted in PD-L1 expression irrespective of disease. Most T cells did not express PD-L1. Using skin samples from 49 additional CTCL patients for an unsupervised analysis of genome-wide mRNA expression profiles corroborated that advanced T3/T4-stage samples expressed more checkpoint inhibition mRNA compared with T1/T2 stage patients or healthy controls. Exhaustion of activated T cells is therefore a hallmark of both CD4+ and CD8+ T cells isolated from the lesional skin of patients with CTCL, with increasing expression as the disease progresses. These results justify identification of antigens driving T-cell exhaustion and the evaluation of immune checkpoint inhibition to reverse T-cell exhaustion earlier in the treatment of CTCL. Cancer Immunol Res; 6(8); 900–9. ©2018 AACR.

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