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Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer.
J Cancer 2020; 11(3):648-656JC

Abstract

Programmed death receptor-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play important roles in tumor immune evasion. PD-1 blockade could produce an effective antitumor effect in many solid tumors except prostate cancer (PCa) because of rare programmed death ligand-1 (PD-L1) expression on PCa cells. Streptavidin (SA)-GM-CSF surface-anchored tumor cell (Anchored GM-CSF) vaccines could increase the number of tumor-infiltrating lymphocytes (TILs) and induce specific antitumor immune responses. The Anchored-GM-CSF vaccine and anti-PD-1 antibodies exerted synergistic effects in mouse models of PCa metastasis. However, the response rate was low due to the presence of other negative regulatory pathways. Tim-3 expression could be upregulated at resistance to combination therapy with anti-PD-1 antibodies and the Anchored GM-CSF vaccine. Sequential administration of anti-PD-1 and anti-Tim-3 antibodies could further improve the efficacy of the Anchored GM-CSF vaccine therapy, and tumor regression was noted in over 60% of animals. This triple therapy improved the specific cytotoxic activity, proliferation and secretion of CD8+ TILs and reduced the production of tumor-promoting cytokines. These findings indicated that this triple therapy could induce a robust antitumor immune response in mouse models of PCa.

Authors+Show Affiliations

Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Radiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Radiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Radiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.Department of Radiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde District, Foshan), Foshan, 528300, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31942188

Citation

Zhang, Xinji, et al. "Increased Tim-3 Expression On TILs During Treatment With the Anchored GM-CSF Vaccine and anti-PD-1 Antibodies Is Inversely Correlated With Response in Prostate Cancer." Journal of Cancer, vol. 11, no. 3, 2020, pp. 648-656.
Zhang X, Chen H, Li G, et al. Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer. J Cancer. 2020;11(3):648-656.
Zhang, X., Chen, H., Li, G., Zhou, X., Shi, Y., Zou, F., ... Long, Z. (2020). Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer. Journal of Cancer, 11(3), pp. 648-656. doi:10.7150/jca.29705.
Zhang X, et al. Increased Tim-3 Expression On TILs During Treatment With the Anchored GM-CSF Vaccine and anti-PD-1 Antibodies Is Inversely Correlated With Response in Prostate Cancer. J Cancer. 2020;11(3):648-656. PubMed PMID: 31942188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased Tim-3 expression on TILs during treatment with the Anchored GM-CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer. AU - Zhang,Xinji, AU - Chen,Haixiong, AU - Li,Guanfeng, AU - Zhou,Xiangyun, AU - Shi,Yuqiang, AU - Zou,Feng, AU - Chen,Yuanxiang, AU - Gao,Jimin, AU - Yang,Shaomin, AU - Wu,Shihao, AU - Long,Zhaolin, Y1 - 2020/01/01/ PY - 2018/09/04/received PY - 2019/08/12/accepted PY - 2020/1/17/entrez PY - 2020/1/17/pubmed PY - 2020/1/17/medline KW - T cell immunoglobulin and mucin domain-containing protein-3 KW - immunotherapy. KW - programmed death receptor-1 KW - prostate cancer KW - vaccine SP - 648 EP - 656 JF - Journal of Cancer JO - J Cancer VL - 11 IS - 3 N2 - Programmed death receptor-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play important roles in tumor immune evasion. PD-1 blockade could produce an effective antitumor effect in many solid tumors except prostate cancer (PCa) because of rare programmed death ligand-1 (PD-L1) expression on PCa cells. Streptavidin (SA)-GM-CSF surface-anchored tumor cell (Anchored GM-CSF) vaccines could increase the number of tumor-infiltrating lymphocytes (TILs) and induce specific antitumor immune responses. The Anchored-GM-CSF vaccine and anti-PD-1 antibodies exerted synergistic effects in mouse models of PCa metastasis. However, the response rate was low due to the presence of other negative regulatory pathways. Tim-3 expression could be upregulated at resistance to combination therapy with anti-PD-1 antibodies and the Anchored GM-CSF vaccine. Sequential administration of anti-PD-1 and anti-Tim-3 antibodies could further improve the efficacy of the Anchored GM-CSF vaccine therapy, and tumor regression was noted in over 60% of animals. This triple therapy improved the specific cytotoxic activity, proliferation and secretion of CD8+ TILs and reduced the production of tumor-promoting cytokines. These findings indicated that this triple therapy could induce a robust antitumor immune response in mouse models of PCa. SN - 1837-9664 UR - https://www.unboundmedicine.com/medline/citation/31942188/Increased_Tim-3_expression_on_TILs_during_treatment_with_the_Anchored_GM-CSF_vaccine_and_anti-PD-1_antibodies_is_inversely_correlated_with_response_in_prostate_cancer L2 - http://www.jcancer.org/v11p0648.htm DB - PRIME DP - Unbound Medicine ER -