Open AccessTumour cell‐intrinsic CTLA 4 regulates PD ‐L1 expression in non‐small cell lung cancer
Author(s) -
Zhang Huijun,
Dutta Pranabananda,
Liu Jinguo,
Sabri Nafiseh,
Song Yuanlin,
Li Willis X.,
Li Jinghong
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13956
Subject(s) - cytotoxic t cell , cancer research , ctla 4 , biology , t cell , lung cancer , immune checkpoint , antibody , cell growth , carcinogenesis , cancer cell , cancer , immune system , immunotherapy , immunology , medicine , in vitro , biochemistry , genetics
Cytotoxic T lymphocyte antigen 4 ( CTLA 4) and programmed cell death protein 1 ( PD ‐1) are immune checkpoint proteins expressed in T cells. Although CTLA 4 expression was found in multiple tumours including non‐small cell lung cancer ( NSCLC ) tissues and cells, its function in tumour cells is unknown. Recently, PD ‐1 was found to be expressed in melanoma cells and to promote tumorigenesis. We found that CTLA 4 was expressed in a subset of NSCLC cell lines and in a subgroup of cancer cells within the lung cancer tissues. We further found that in NSCLC cells, anti‐ CTLA 4 antibody can induce PD ‐L1 expression, which is mediated by CTLA 4 and the EGFR pathway involving phosphorylation of MEK and ERK . In CTLA 4 knockout cells, EGFR knockout cells or in the presence of an EGFR tyrosine kinase inhibitor, anti‐ CTLA 4 antibody was not able to induce PD ‐L1 expression in NSCLC cells. Moreover, anti‐ CTLA 4 antibody promoted NSCLC cell proliferation in vitro and tumour growth in vivo in the absence of adaptive immunity. These results suggest that tumour cell‐intrinsic CTLA 4 can regulate PD ‐L1 expression and cell proliferation, and that anti‐ CTLA 4 antibody, by binding to the tumour cell‐intrinsic CTLA 4, may result in the activation of the EGFR pathway in cancer cells.