The CD39/CD73 adenosinergic pathway is increased by proinflammatory states and modified by chemo-radiation in human non-small cell lung cancer.

Authors

Kerryan Ashley, Alicia Ding, Mohammad Arammash, Krishna Iyer, Kishu Ranjan, Barani Kumar Rajendran, Boyu Huang, Daniel Boiarsky, Roy Herbst, Sarah Goldberg, Kurt A Schalper

Published in

Cell reports. Medicine. Pages 103139. Nov 09, 2026. Epub Nov 09, 2026.

Abstract

Recent clinical trials show prominent anti-tumor activity of CD73-blocking antibodies in combination with programmed death-ligand 1 (PD-L1) antagonists in a subset of patients with resectable non-small cell lung cancer (NSCLC), which highlights the need to understand the properties of the CD39/CD73 pathway in human lung malignancies and its modulation by other anti-cancer therapies. To address this, we study the distribution, biological context, spatial heterogeneity, clinical significance, and modulation of CD39/CD73 using multiplexed quantitative immunofluorescence and spatial transcriptomics analysis of multiple NSCLC patient cohorts, as well as in vitro experiments of cultured NSCLC cells. Our results reveal an asymmetric distribution of the CD39/CD73 pathway within the tumor microenvironment, preferential expression in lung adenocarcinomas with elevated PD-L1 and effector T cell infiltration or lacking STK11/KEAP1 mutations, limited intratumor spatial heterogeneity, and differential modulation of cancer cell CD73 by proinflammatory cytokines and systemic radio-chemotherapy. Collectively, our results can inform optimal design of therapeutic interventions and patient selection strategies.

PMID:
43003091
Bibliographic data and abstract were imported from PubMed on 10 Nov 2026.

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