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Carboplatin enhances lymphocyte-endothelial interactions to promote CD8

Authors :
Jaron, Mark
Dan T, Fisher
Minhyung, Kim
Tiffany, Emmons
A N M Nazmul, Khan
Emad, Alqassim
Kelly, Singel
Anna, Mistarz
Amit, Lugade
Haiying, Zhan
Han, Yu
Brahm, Segal
Shashikant, Lele
Peter, Frederick
Danuta, Kozbor
Joseph, Skitzki
Kunle, Odunsi
Source :
Gynecologic oncology. 168
Publication Year :
2022

Abstract

Standard chemotherapy agents, including carboplatin, have known immunogenic properties. We sought to determine how carboplatin may influence lymphocyte trafficking to tumor sites.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.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.These novel findings suggest a role for chemotherapeutic agents to broadly influence anti-tumor immune responses beyond the induction of immunogenic tumor cell death.

Details

ISSN :
10956859
Volume :
168
Database :
OpenAIRE
Journal :
Gynecologic oncology
Accession number :
edsair.pmid..........9a68bbb6f43f3684fdcb1998d7032681