Next Article in Journal
Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products—APRIL and TACI Molecules
Next Article in Special Issue
Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation—A Special Reference to Colorectal Cancer
Previous Article in Journal
High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection
Article

The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer

1
Graduate Biomedical Sciences, University of Alabama at Birmingham (UAB), Birmingham, AL 35233, USA
2
Department of Nutrition Sciences, UAB, Birmingham, AL 35233, USA
3
School of Nursing, UAB, Birmingham, AL 35233, USA
4
Nutrition Obesity Research Center, UAB, Birmingham, AL 35233, USA
5
O’Neal Comprehensive Cancer Center, UAB, Birmingham, AL 35233, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(10), 2872; https://doi.org/10.3390/cancers12102872
Received: 14 August 2020 / Revised: 28 September 2020 / Accepted: 5 October 2020 / Published: 6 October 2020
(This article belongs to the Special Issue Breakthroughs in Cancer-Related Immunotherapy)
Although immune-stimulatory and targeted therapies benefit many patients with metastatic kidney cancer, a sizeable proportion of patients fail to respond. Recent studies in mice demonstrate that nutrient-limiting dietary interventions can improve responses to chemotherapy. However, these studies did not investigate effects on metastasis, and the impact of these interventions on the response to immunotherapy or targeted therapies in kidney cancer is unknown. We therefore studied the effects of a glucose-limiting drug called acarbose, which is used to treat type 2 diabetes, in a spontaneously-metastasizing mouse model of kidney cancer. We found that acarbose slowed kidney cancer growth and promoted protective immune responses. In combination with either an immunotherapy or a targeted therapy used clinically to treat kidney cancer, acarbose led to improved treatment outcomes and reduced lung metastases. Our findings contribute to the emerging idea of using nutrition-based interventions to enhance responses to cancer treatments.
Although immune checkpoint inhibitors and targeted therapeutics have changed the landscape of treatment for renal cell carcinoma (RCC), most patients do not experience significant clinical benefits. Emerging preclinical studies report that nutrition-based interventions and glucose-regulating agents can improve therapeutic efficacy. However, the impact of such agents on therapeutic efficacy in metastatic kidney cancer remains unclear. Here, we examined acarbose, an alpha-glucosidase inhibitor and antidiabetic agent, in a preclinical model of metastatic kidney cancer. We found that acarbose blunted postprandial blood glucose elevations in lean, nondiabetic mice and impeded the growth of orthotopic renal tumors, an outcome that was reversed by exogenous glucose administration. Delayed renal tumor outgrowth in mice on acarbose occurred in a CD8 T cell-dependent manner. Tumors from these mice exhibited increased frequencies of CD8 T cells that retained production of IFNγ, TNFα, perforin, and granzyme B. Combining acarbose with either anti-PD-1 or the mammalian target of rapamycin inhibitor, rapamycin, significantly reduced lung metastases relative to control mice on the same therapies. Our findings in mice suggest that combining acarbose with current RCC therapeutics may improve outcomes, warranting further study to determine whether acarbose can achieve similar responses in advanced RCC patients in a safe and likely cost-effective manner. View Full-Text
Keywords: kidney cancer; glucose; immunity; nutrition; immunotherapy kidney cancer; glucose; immunity; nutrition; immunotherapy
Show Figures

Figure 1

MDPI and ACS Style

Orlandella, R.M.; Turbitt, W.J.; Gibson, J.T.; Boi, S.K.; Li, P.; Smith, D.L., Jr.; Norian, L.A. The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer. Cancers 2020, 12, 2872. https://doi.org/10.3390/cancers12102872

AMA Style

Orlandella RM, Turbitt WJ, Gibson JT, Boi SK, Li P, Smith DL Jr., Norian LA. The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer. Cancers. 2020; 12(10):2872. https://doi.org/10.3390/cancers12102872

Chicago/Turabian Style

Orlandella, Rachael M., William J. Turbitt, Justin T. Gibson, Shannon K. Boi, Peng Li, Daniel L. Smith Jr., and Lyse A. Norian. 2020. "The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer" Cancers 12, no. 10: 2872. https://doi.org/10.3390/cancers12102872

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop