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

卡铂增强淋巴细胞-内皮细胞相互作用,促进 CD8+ T 细胞运输至卵巢肿瘤微环境

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作者: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

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.

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.

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