Lung cancer (Amsterdam, Netherlands) · 2020
Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells.
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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
Аннотация
BACKGROUND: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.