Tumor-infiltrating T-regulatory cells adapt to altered metabolism to promote tumor-immune escape

Abstract

Tumor mass and its microenvironment alter host immune system in various ways to promote tumor growth. One of the modifications is evasion of immune surveillance by augmenting the number of Tregs in tumor vicinity. Elevated levels of Tregs are seen in peripheral circulation and tumor tissue of cancer patients. Cancer cells release several chemokines to attract Tregs in tumor-site. Infiltration of Tregs has clinical significance because being immunosuppressive infiltrating Tregs suppress other immune cells making the tumor microenvironment favorable for tumor growth. On the other hand, infiltrating Tregs show metabolic alteration in tumor microenvironment which allows their selective survival over the others. Persistence of Tregs in the tumor microenvironment and subsequent immunosuppression makes Tregs a potential therapeutic obstacle and the reason behind the failure of immunotherapy. In this review, we emphasize the recent development in the metabolic adaptation of tumor-infiltrating Tregs and the therapeutic approaches to boost immunity against cancer.

Graphical abstract

In tumor microenvironment, cancer cells show increased uptake of available glucose and metabolically change the environment. Effector T cells often cannot adapt to the glucose-depleted metabolic environment created by cancer cells and thus fail to survive. In the contrary, immunosuppressive Tregs which are infiltrated in the tumor by the tumor-derived chemokine gradient survive this inhospitable environment and facilitate tumor immune-evasion. The Tregs adapt to the glucose-depleted tumor microenvironment by shifting their metabolic preferences from glucose to fatty acid (Created in BioRender.com).