Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.

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Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.

Oncoimmunology. 2018;7(4):e1408747

Authors: Du S, McCall N, Park K, Guan Q, Fontina P, Ertel A, Zhan T, Dicker AP, Lu B

Abstract
Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are emerging. We present a case of NSCLC, who rapidly progressed during a trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy demonstrated PD-1 expression by NSCLC cells. We validated this observation by detecting PD-1 transcript in lung cancer cells and by co-localizing PD-1 and lung cancer-specific markers in resected lung cancer tissues. We further investigated the biological role of cancer-intrinsic PD-1 in a mouse lung cancer cell line, M109. Knockout or antibody blockade of PD-1 enhanced M109 viability in-vitro, while PD-1 overexpression and exposure to recombinant PD-L1 diminished viability. PD-1 blockade accelerated growth of M109-xenograft tumors with increased proliferation and decreased apoptosis in immune-deficient mice. This represents a first-time report of NSCLC-intrinsic PD-1 expression and a potential mechanism by which PD-1 blockade may promote cancer growth.

PMID: 29632720 [PubMed]

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