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Publication : Antibodies against endogenous retroviruses promote lung cancer immunotherapy.

First Author	Ng KW	Year	2023
Journal	Nature	Volume	616
Issue	7957	Pages	563-573
PubMed ID	37046094	Mgi Jnum	J:340017
Mgi Id	MGI:7525551	Doi	10.1038/s41586-023-05771-9
Citation	Ng KW, et al. (2023) Antibodies against endogenous retroviruses promote lung cancer immunotherapy. Nature 616(7957):563-573

abstractText

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)(1,2). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive(1,2). Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma(3). We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.

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Publication : Antibodies against endogenous retroviruses promote lung cancer immunotherapy.

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