Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 15;12(10):2983.
doi: 10.3390/cancers12102983.

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Ravindra Pramod Deshpande  1 , Sambad Sharma  1 , Kounosuke Watabe  1
Affiliations
Review

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Ravindra Pramod Deshpande et al. Cancers (Basel). .

Abstract

Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.

Keywords: anti PD-L1; anti-CTLA; circadian rhythms; diabetes; diet; immunotherapy; obesity.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Various lifestyle and metabolic factors affect CPI effectiveness.
Figure 2
Figure 2
Ageing reduces responsiveness to CPI.
Figure 3
Figure 3
Effect of diet on CPI response.
Figure 4
Figure 4
Secondary effects of immunotherapy response.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kalbasi A., Ribas A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 2020;20:25–39. doi: 10.1038/s41577-019-0218-4. - DOI - PMC - PubMed
    1. Singh P.P., Sharma P.K., Krishnan G., Lockhart A.C. Immune checkpoints and immunotherapy for colorectal cancer. Gastroenterol. Rep. 2015;3:289–297. doi: 10.1093/gastro/gov053. - DOI - PMC - PubMed
    1. Freeman G.J., Long A.J., Iwai Y., Bourque K., Chernova T., Nishimura H., Fitz L.J., Malenkovich N., Okazaki T., Byrne M.C., et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000;192:1027–1034. doi: 10.1084/jem.192.7.1027. - DOI - PMC - PubMed
    1. Butte M.J., Keir M.E., Phamduy T.B., Sharpe A.H., Freeman G.J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27:111–122. doi: 10.1016/j.immuni.2007.05.016. - DOI - PMC - PubMed
    1. Blackburn S.D., Shin H., Haining W.N., Zou T., Workman C.J., Polley A., Betts M.R., Freeman G.J., Vignali D.A., Wherry E.J. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 2009;10:29–37. doi: 10.1038/ni.1679. - DOI - PMC - PubMed