Immune Microenvironment Remodeling After Radiation of a Progressing Brain Metastasis

Authors

William H Hudson
Jeffrey J Olson
Lisa J Sudmeier

Publication Date

6-20-2023

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2023.101054

PMID

37209684

PMCID

PMC10313918

PubMedCentral® Posted Date

5-19-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Brain Neoplasms, Brain, T-Lymphocytes, Tumor Microenvironment, cancer immunotherapy, T cells, CD8+ T cells, CD4+ T cells, lung cancer, radiation, stereotactic radiosurgery, brain metastasis, metastasis, single-cell RNA sequencing

Abstract

Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, radiation is associated with the depletion of exhausted, tumor-resident T cell clones and their replacement by circulating clones unlikely to contribute to tumor-specific immunity. These results provide insight into the local effects of radiation on anti-tumor immunity and raise important considerations for the combination of radiation and immunotherapy.

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