CD200 blockade modulates tumor immune microenvironment and fails to show efficacy in inhibiting tumor growth in a murine model of melanoma

Talebian, Fatemeh; Yu, Jinpeng; Lynch, Katherine N.; Jq, Liu; Carson, W. E.; Bai, Xia

doi:10.21417/ft2021fcdb

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“…Consistent with these studies, our results indicated that CD200 + CTLs are critical to effective PD-1/PD-L1 blockade therapy because depletion of CD200 + CTLs by anti-CD200 antibodies abrogated tumor control by PD-L1 therapy. Our results are supported by a study showing that tumors from anti-CD200–treated mice had decreased immune cell infiltration and T cell receptor clonality ( 41 ). However, another study showed that anti-CD200 antibody treatment reduces tumor burden in a subcutaneously inoculated MT5 tumor model [KPC (K-ras LSL.G12D/+ ; Trp53 R172H/+ ; Pdx-1-Cre)–derived cancer cell line, mouse pancreatic cancer] ( 21 ).…”

Section: Discussionsupporting

confidence: 85%

CD200 ⁺ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

Wang

Zha

et al. 2023

Sci. Transl. Med.

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Anti–PD-1/PD-L1 therapy, either by anti–PD-1 antibody or anti–PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8 + T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8 + T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200 + cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200 + T cells positively related to a favorable clinical outcome to anti–PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200 + CTLs are essential for efficacious anti–PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200 + CTLs and found that these cells are enriched for tumor antigen–specific CTLs and have antitumor effector functions. Coinoculation of CD200 + CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200 + CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200 + CTLs in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.

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Section: Discussionsupporting

confidence: 85%

CD200 ⁺ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

Wang

Zha

et al. 2023

Sci. Transl. Med.

View full text Add to dashboard Cite

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CD200 blockade modulates tumor immune microenvironment and fails to show efficacy in inhibiting tumor growth in a murine model of melanoma

Cited by 1 publication

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CD200 ⁺ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

CD200 ⁺ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

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CD200 blockade modulates tumor immune microenvironment and fails to show efficacy in inhibiting tumor growth in a murine model of melanoma

Cited by 1 publication

References 0 publications

CD200 + cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

CD200 + cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

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CD200 ⁺ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy

CD200 ⁺ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy