Are tumor-associated carbohydrates the missing link between the gut microbiome and response to immune checkpoint inhibitor treatment in cancer?

ABSTRACT

Immune checkpoint inhibitor therapy has dramatically improved survival in a significant subset of patients with several solid tumor types. Increasing the number of patients benefitting from this form of therapy is an important translational research goal. Correlations between the composition of the gut microbiome and response to immune checkpoint inhibitor therapy raised the possibility that direct modulation of the gut microbiome may significantly improve the clinical benefit of this treatment. Several lines of observations suggest that tumor-associated carbohydrates, including those recognized as blood group-related glycolipid antigens, such as the Forssman antigen, may be some of the key factors behind this clinical correlation. Such antigens are expressed in human cancer, humans often produce antibodies against those, and they can induce antibody directed cellular cytotoxicity. Importantly, these antibodies are often induced by antigens present in microbes of the gut. If identified, these antibodies could be boosted by appropriate vaccination techniques and thus enhance anti-tumor immunity with minimal side effects.

KEYWORDS:

• Immune checkpoint inhibitor therapy
• gut microbiome
• glycolipid antigens
• antibody directed cellular cytotoxicity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Z.S. was supported by the Department of Defence, Congressionally Directed Medical Research Programs (award number is W81XWH-18-1-0751 and W81XWH-22-1-0089) and the Breast Cancer Research Foundation (BCRF-22-159). J.M. was supported by the Hungarian National Research, Development and Innovation Office, K-147226. The figure was created with BioRender.com.