Du et al. describe a patient with non-small cell lung cancer who rapidly progressed after treatment with radiotherapy and anti-PD-1, and was found to have PD-1 expressed on the tumor. In a murine PD-1-expressing M109 lung cancer cell line, knocking out or blocking PD-1 increased cell viability, while overexpressing PD-1 or treating with soluble PD-L1 reduced viability in vitro; PD-1 blockade accelerated M109 tumor growth in vivo. Tumor-intrinsic PD-1 expression was observed in about 3-10% of lung cancer tissue samples examined.
Anti-PD-1 immunotherapy is the standard of care for treating many patients with nonsmall
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.
Author Info: (1) Department of Radiation Oncology, Thomas Jefferson University (2) Department of Radiation Oncology, Thomas Jefferson University (3) Department of Radiation Oncology, Thomas Je
Author Info: (1) Department of Radiation Oncology, Thomas Jefferson University (2) Department of Radiation Oncology, Thomas Jefferson University (3) Department of Radiation Oncology, Thomas Jefferson University (4) Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center (5) Department of Cancer Biology, Thomas Jefferson University (6) Department of Cancer Biology, Thomas Jefferson University (7) Department of Pharmacology and Experimental Therapeutics, Division of Biostatistics Thomas Jefferson University (8) (9) Department of Radiation Oncology, Thomas Jefferson University (10) Department of Radiation Oncology, Thomas Jefferson University
