5 Stereotactic Body Radiation Therapy Enriches Mediators of Humoral Immune Activity in Metastatic Renal Cell Carcinoma

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Stereotactic body radiation therapy (SBRT) enriches mature B cell subtypes and humoral immune activity in the tumor microenvironment of metastatic renal cell carcinoma, which is associated with improved responsiveness to immune checkpoint blockade. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Nicholas Salgia; Adil Khan; Mark Long; J.S. Chow; Gavin Twoey; Kyle Leatt; Yu Fujiwara; Scott Abrams; Thomas Schwaab; Anurag Singh; Jason Muhitch

doi:10.1093/oncolo/oyag312.006

September 1, 2026The OncologistOpen Access

5 Stereotactic Body Radiation Therapy Enriches Mediators of Humoral Immune Activity in Metastatic Renal Cell Carcinoma

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Key Points

To determine how stereotactic body radiation therapy affects humoral immunity and B cell phenotypes within the tumor microenvironment of metastatic renal cell carcinoma.
Analyzed primary renal cell carcinoma tissue from patients treated with 15 Gy stereotactic body radiation therapy (NCT01892930) versus matched controls using bulk RNA sequencing (n=8 per arm), single-cell RNA sequencing (n=4 treated vs. n=2 control; 37,029 cells), and 17-marker flow cytometry (n=5 treated vs. n=8 control).
Assessed B cell receptor repertoires with TRUST4 and correlated B cell subsets with immune checkpoint blockade response using transcriptomic data from the IMmotion151 (n=757) and HCRN-GU16-260 (n=70) cohorts.
Bulk RNA sequencing demonstrated significant enrichment in radiation-treated tumors for B cell maturation pathways (all padj < 1x10^-25), total B cells (p = 0.002), and class-switched memory B cells (p = 0.010).
Flow cytometry identified an increased abundance of CD38+ IgD- antibody-producing B cells post-radiation (p = 0.006), consistent with single-cell RNA sequencing showing higher plasma cell proportions (15.3% vs. 6.5%).
Transcriptomic deconvolution of IMmotion151 and HCRN-GU16-260 cohorts linked class-switched memory B cells with objective response to immune checkpoint blockade (p = 0.009 and p = 0.020, respectively).

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Implication

Demonstrates that stereotactic body radiation therapy enriches mature B cells in renal cell carcinoma, indicating potential synergy with checkpoint inhibitors.

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Cite This Study

Salgia et al. (2026) studied this question.

synapsesocial.com/papers/6a99365f636c6408cfa7f876 https://doi.org/10.1093/oncolo/oyag312.006

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5 Stereotactic Body Radiation Therapy Enriches Mediators of Humoral Immune Activity in Metastatic Renal Cell Carcinoma

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5 Stereotactic Body Radiation Therapy Enriches Mediators of Humoral Immune Activity in Metastatic Renal Cell Carcinoma

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