Language
English
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
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.
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
Published Open-Access
yes
Recommended Citation
, "Immune Microenvironment Remodeling After Radiation of a Progressing Brain Metastasis" (2023). Faculty, Staff and Students Publications. 1993.
https://digitalcommons.library.tmc.edu/baylor_docs/1993