Non-classical Monocytes Enhance the Efficacy of Immune Checkpoint Inhibitors on Colon Cancer in a Syngeneic Mouse Model

Tsubasa Goshima; Katsuaki Ieguchi; Nobuyuki Onishi; Takashi Shimizu; Daisuke Takayanagi; Makoto Watanabe; Yuki Fujimoto; Ryotaro Ohkuma; Risako Suzuki; Toshiaki Tsurui; Emiko Mura; Nana Iriguchi; Tomoyuki Ishiguro; Masahiro Shimokawa; Yuya Hirasawa; Yutaro Kubota; Hirotsugu Ariizumi; Atsushi Horiike; Kiyoshi Yoshimura; Mayumi Tsuji; Yuji Kiuchi; Shinichi Kobayashi; Jun Fujishiro; Robert M Hoffman; Takuya Tsunoda; Satoshi Wada

doi:10.21873/anticanres.16784

Non-classical Monocytes Enhance the Efficacy of Immune Checkpoint Inhibitors on Colon Cancer in a Syngeneic Mouse Model

Anticancer Res. 2024 Jan;44(1):23-29. doi: 10.21873/anticanres.16784.

Authors

Tsubasa Goshima^{1

2

3}, Katsuaki Ieguchi^{1

4}, Nobuyuki Onishi^{1

4}, Takashi Shimizu^{1

4}, Daisuke Takayanagi^{1

2

4}, Makoto Watanabe^{1

4

5

6}, Yuki Fujimoto^{1

2

4}, Ryotaro Ohkuma², Risako Suzuki², Toshiaki Tsurui^{2

5

6}, Emiko Mura², Nana Iriguchi², Tomoyuki Ishiguro², Masahiro Shimokawa², Yuya Hirasawa², Yutaro Kubota², Hirotsugu Ariizumi², Atsushi Horiike², Kiyoshi Yoshimura^{2

4

7}, Mayumi Tsuji⁶, Yuji Kiuchi^{5

6}, Shinichi Kobayashi⁴, Jun Fujishiro³, Robert M Hoffman^{8

9}, Takuya Tsunoda², Satoshi Wada^{10

2

4}

Affiliations

¹ Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.
² Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.
³ Department of Pediatric Surgery, The University of Tokyo Hospital, Tokyo, Japan.
⁴ Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.
⁵ Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
⁶ Pharmacological Research Center, Showa University, Tokyo, Japan.
⁷ Department of Clinical ImmunoOncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.
⁸ AntiCancer Inc., San Diego, CA, U.S.A.
⁹ Department of Surgery, University of California, San Diego, CA, U.S.A.
¹⁰ Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan; st-wada@med.showa-u.ac.jp.

PMID: 38159965
DOI: 10.21873/anticanres.16784

Abstract

Background/aim: The response rate to immune checkpoint inhibitors (ICIs) is approximately 10%-30% and only in a few cancer types. In the present study, we determined whether non-classical monocytes (NCMs) could enhance ICI efficacy in colon cancer using a syngeneic mouse model.

Materials and methods: The MC38 C57BL/6 mouse colon cancer model was used. Cells collected from the bone marrow of C57BL/6 mice were cultured, and NCMs were fractionated by cell sorting and administered via the tail veins to the mice implanted with MC38 cells. The anti-mouse PD-L1 antibody was administered three times, and tumor volume and overall survival were observed.

Results: More tumors were eradicated and more complete response occurred, after cotreatment with ICIs and NCMs than after treatment with ICIs alone. Moreover, no efficacy was observed when NCMs were administered alone.

Conclusion: NCMs enhance ICI efficacy. The underlying mechanisms and clinical applications will be studied in the future.

Keywords: Immune checkpoint inhibitor; flow cytometry; non-classical monocyte; overall survival.

MeSH terms

Animals
B7-H1 Antigen
Colonic Neoplasms* / drug therapy
Disease Models, Animal
Immune Checkpoint Inhibitors* / pharmacology
Immune Checkpoint Inhibitors* / therapeutic use
Mice
Mice, Inbred C57BL
Monocytes

Substances

Immune Checkpoint Inhibitors
B7-H1 Antigen