Anti-tumor effects of anti-programmed cell death-1 antibody treatment are attenuated in streptozotocin-induced diabetic mice.

Abstract

Hyperglycemia impairs immune response; however, it remains unknown whether the anti-tumor effects of anti-programmed cell death-1 antibody (PD-1-Ab) treatment are changed in hyperglycemic conditions. We analyzed the effect of PD-1-Ab on tumor growth in streptozotocin-induced diabetic mice (STZ-mice) subcutaneously inoculated with MC38 (a colon carcinoma cell line). Furthermore, we assessed the expression of chemokines by polymerase chain reaction (PCR) array in tumor-draining lymph nodes (dLNs) of these mice and MC38 cells cultured in different glucose concentrations. The suppressive effect of PD-1-Ab on tumor growth was attenuated. This was accompanied by fewer tumor-infiltrating CD8+ T cells, and STZ-mice had fewer tumor-infiltrating CD11c+ dendritic cells (DCs) than normoglycemic mice. mRNA expression levels of CXCL9, a chemokine recruiting CD8+ T cells, were lower in dLNs of STZ-mice than in normoglycemic mice after PD-1-Ab treatment, and its protein was expressed in DCs. In MC38 cells cultured with 25 mM glucose, mRNA expression of CCL7, a chemokine recruiting DCs, was decreased compared to cells cultured with 5 mM glucose. These results suggest that the STZ-induced hyperglycemia impairs the effect of PD-1-Ab treatment on MC38 tumor growth, and is accompanied by reduced infiltration of DCs and CD8+ T cells and decreased expression of CCL7 and CXCL9.

• Authors: Masaaki Ito, Shintaro Iwama, Daisuke Sugiyama, Yoshinori Yasuda, Takayuki Okuji, Tomoko Kobayashi, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Hiroyoshi Nishikawa, Hiroshi Arima
• Journal: Scientific reports (Sci Rep) Vol. 13 Issue 1 Pg. 5939 (04 12 2023) ISSN: 2045-2322 [Electronic] England
• PMID: 37046033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Programmed Cell Death 1 Receptor
• RNA, Messenger
• Streptozocin
• Pdcd1 protein, mouse

Topics

• Animals
• Mice
• CD8-Positive T-Lymphocytes
• Cell Death
• Cell Line, Tumor
• Dendritic Cells
• Diabetes Mellitus, Experimental (drug therapy)
• Hyperglycemia
• Mice, Inbred C57BL
• Neoplasms (pathology)
• Programmed Cell Death 1 Receptor (metabolism)
• RNA, Messenger
• Streptozocin