Carboplatin enhances lymphocyte-endothelial interactions to promote CD8+ T cell trafficking into the ovarian tumor microenvironment

ElsevierVolume 168, January 2023, Pages 92-99Gynecologic OncologyAuthor links open overlay panelHighlights•

Carboplatin promotes lymphocyte adhesive interactions with tumor vasculature and increases lymphocyte trafficking.

Carboplatin was associated with increased vessel diameters and percentage of viable tumor vessels supporting blood flow.

The influence of carboplatin on the tumor microenvironment suggests synergy with existing immunotherapy approaches.

AbstractObjectives

Standard chemotherapy agents, including carboplatin, have known immunogenic properties. We sought to determine how carboplatin may influence lymphocyte trafficking to tumor sites.

Methods

Murine models of ovarian cancer were utilized to examine lymphocyte trafficking with common clinically used agents including carboplatin, anti-PD-1 antibody, or anti-VEGFR-2 antibody. Adhesion interactions of lymphocytes with tumor vasculature were measured using intravital microscopy, lymphocyte homing with immunohistochemistry, and treatment groups followed for overall survival.

Results

Carboplatin chemotherapy profoundly alters the tumor microenvironment to promote lymphocyte adhesive interactions with tumor vasculature and resultant improvement in lymphocyte trafficking. The measured results seen with carboplatin in the tumor microenvironment were superior to anti-PD-1 treatment or anti-VEGFR-2 which may have contributed to increased overall survival in carboplatin treated groups.

Conclusions

These novel findings suggest a role for chemotherapeutic agents to broadly influence anti-tumor immune responses beyond the induction of immunogenic tumor cell death.

Keywords

Ovarian cancer

Tumor immunology

Lymphocyte trafficking

Tumor infiltrating lymphocytes

Antiangiogenic therapy

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© 2022 Published by Elsevier Inc.

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