Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells

•CDDP/PEM enhanced anti-tumor effects of anti-PD-1 antibody against MPM in mice.•CDDP/PEM decreased intratumoral myeloid-derived suppressor cells (MDSCs).•CDDP/PEM reduced VEGF in MPM cells, which is a chemotactic factor for MDSCs. The combination of anti-PD-1/PD-L1 antibody with chemotherapy has be...

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Bibliographic Details
Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2020-08, Vol.146, p.86-96
Main Authors: Otsuka, Kenji, Mitsuhashi, Atsushi, Goto, Hisatsugu, Hanibuchi, Masaki, Koyama, Kazuya, Ogawa, Hirohisa, Ogino, Hirokazu, Saijo, Atsuro, Kozai, Hiroyuki, Yoneda, Hiroto, Tobiume, Makoto, Kishuku, Masatoshi, Ishizawa, Keisuke, Nishioka, Yasuhiko
Format: Article
Language:English
Subjects:
Lung cancer
Malignant pleural mesothelioma
MDSC
PD-1
VEGF
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Summary:•CDDP/PEM enhanced anti-tumor effects of anti-PD-1 antibody against MPM in mice.•CDDP/PEM decreased intratumoral myeloid-derived suppressor cells (MDSCs).•CDDP/PEM reduced VEGF in MPM cells, which is a chemotactic factor for MDSCs. The combination of anti-PD-1/PD-L1 antibody with chemotherapy has been approved for the first-line therapy of lung cancer. However, the effects against malignant mesothelioma (MPM) and the immunological mechanisms by which chemotherapy enhances the effect of targeting PD-1/PD-L1 in MPM are poorly understood. We utilized syngeneic mouse models of MPM and lung cancer and assessed the therapeutic effects of anti-PD-1 antibody and its combination with cisplatin (CDDP) and pemetrexed (PEM). An immunological analysis of tumor-infiltrating cells was performed with immunohistochemistry. We observed significant therapeutic effects of anti-PD-1 antibody against MPM. Although the effect was associated with CD8+ and CD4+ T cells in tumors, the number of Foxp3+ cells was not reduced but rather increased. Consequently, combination with CDDP/PEM significantly enhanced the antitumor effects of anti-PD-1 antibody by decreasing numbers of intratumoral myeloid-derived suppressor cells (MDSCs) and vessels probably through suppression of VEGF expression by CDDP + PEM. The combination of anti-PD-1 antibody with CDDP + PEM may be a promising therapy for MPM via inhibiting the accumulation of MDSCs and vessels in tumors.
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2020.05.023