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The Effects of 6 Common Antidiabetic Drugs on Anti-PD1 Immune Checkpoint Inhibitor in Tumor Treatment.

ABSTRACT: Diabetes and cancer are common diseases and are frequently diagnosed in the same individual. These patients need to take antidiabetic drugs while receiving antitumor drugs therapy. Recently, immunotherapy offers significant advances for cancer treatment. However, it is unclear whether antidiabetic drugs affect immunotherapy. Here, by employing syngeneic mouse colon cancer model and melanoma model, we studied the effects of 6 common antidiabetic drugs on anti-PD1 immune checkpoint inhibitor in tumor treatment, including acarbose, sitagliptin, metformin, glimepiride, pioglitazone, and insulin. We found that acarbose and sitagliptin enhanced the tumor inhibition of anti-PD1, and metformin had no effect on the tumor inhibition of anti-PD1, whereas glimepiride, pioglitazone, and insulin weakened the tumor inhibition of anti-PD1. Our study suggests that cancer patients receiving anti-PD1 antibody therapy need serious consideration when choosing antidiabetic drugs. In particular, acarbose significantly inhibited tumor growth and further enhanced the therapeutic effect of anti-PD1, which can be widely used in tumor therapy. Based on this study, further clinical trials are expected.

SUBMITTER: Zhan ZT

PROVIDER: S-EPMC9410852 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The Effects of 6 Common Antidiabetic Drugs on Anti-PD1 Immune Checkpoint Inhibitor in Tumor Treatment.

Zhan Ze-Tao ZT Liu Lu L Cheng Ming-Zhen MZ Gao Yi Y Zhou Wei-Jie WJ

Journal of immunology research 20220818

Diabetes and cancer are common diseases and are frequently diagnosed in the same individual. These patients need to take antidiabetic drugs while receiving antitumor drugs therapy. Recently, immunotherapy offers significant advances for cancer treatment. However, it is unclear whether antidiabetic drugs affect immunotherapy. Here, by employing syngeneic mouse colon cancer model and melanoma model, we studied the effects of 6 common antidiabetic drugs on anti-PD1 immune checkpoint inhibitor in tu ...[more]

PMID: 36033393

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Project description:Anti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic subtype can function as predictive biomarkers for anti-PD1±anti-CTLA4 ICI in patients with advanced melanoma. We performed a single-center retrospective cohort analysis of patients who received anti-PD1±anti-CTLA4 ICI for advanced melanoma between 2012 and 2019. Primary tumor type, BRAF and NRAS mutation status, and other covariates were abstracted from chart review. Log-rank tests and multivariable Cox regression models were used to assess differences in clinical progression-free (cPFS) and overall survival (OS). We identified 230 patients who received 249 lines of anti-PD1±anti-CTLA4 ICI for unresectable or metastatic disease. Of these patients, 74% were cutaneous, 11% mucosal, 8% unknown primary and 7% acral. BRAF and NRAS mutations were identified in 35% and 28% of patients, respectively. In multivariable analyses of the entire cohort, acral or mucosal primary tumor type, >3 metastatic sites, elevated LDH were predictive of shorter cPFS and OS. Combination ICI therapy was associated with longer cPFS (HR 0.57, 95% CI 0.38 to 0.86, p=0.007) and OS (HR 0.42, 95% CI 0.28 to 0.65, p<0.001). Combination ICI was significantly associated with longer OS in unknown primary and mucosal melanoma. There was a non-significant trend toward longer OS with anti-PD1+anti-CTLA4 in cutaneous melanoma, but not in acral melanoma. In multivariable analyses, combination ICI was associated with longer OS in NRAS (HR 0.24, 95% CI 0.10 to 0.62, p=0.003, n=69) and BRAF V600E/K (HR 0.47, 95% CI 0.24 to 0.90, p=0.024, n=86) mutant melanoma but not BRAF/NRAS wild-type (n=94) melanoma. In our cohort, primary melanoma tumor type and genomic subtype were independent predictive markers of cPFS and OS for patients with metastatic melanoma receiving anti-PD1 ICI. Primary tumor type and genomic subtype-including NRAS-should be further evaluated in prospective clinical trials to determine their value as predictive markers. Biologic subtypes may facilitate clinical decision-making when recommending combination ICI treatment (anti-PD1±anti-CTLA4) versus anti-PD1 alone for patients with metastatic melanoma.

Dataset Information

The Effects of 6 Common Antidiabetic Drugs on Anti-PD1 Immune Checkpoint Inhibitor in Tumor Treatment.

Publications

The Effects of 6 Common Antidiabetic Drugs on Anti-PD1 Immune Checkpoint Inhibitor in Tumor Treatment.

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