Immunity journal review by Ho Lab

Three questions to post-doctorate co-authors Pei-Chun Hsueh and Jaeoh Park.

What was the topic and the scope you set yourself going into this review?

Our review* is related to CD8+ T cells, tumor microenvironment, tissue-resident memory T cells and metabolic regulation.We wanted to focus on the metabolic adaptations of CD8+ T cells related to common or unique tumor microenvironmental factors among different origins of the cancer types, and how these factors guide CD8+ T cell anti-tumor immunity.

We hope it can pave the way for a better understanding of the metabolic regulation of CD8+ T cell differentiation and anti-tumor immunity.

Why pay particular attention to this subject?

Although CD8+ T cells are trustworthy soldiers of the fight against cancers, their proliferation and functionality within the tumor microenvironment is largely dampened. To this end, checkpoint blockade has revolutionized the mode of cancer therapy, while many cancers still remain unresponsive to checkpoint blockade. Over the past years, many studies have scrutinised the metabolism of T cells within the TME to provide strategies that boost anti-tumor immunity. Indeed, targeting metabolism seems like a promising way to improve therapeutic efficiencies of the treatment. However, one aspect that should also be highlighted is the diversity of microenvironments. As with the studies encompassed in this review, we paid attention to the diversity and heterogeneity of cancers across different tissues, which might instruct anti-tumor immunity in a different way. Inspired by tissue-resident memory T cells that adapt specifically to the tissue microenvironment, we speculated that tumor-specific T cells might also face a unique environment of tissues which they infiltrate, and may be programmed distinctly from those that infiltrate into different tissues.

What are the hypotheses/models that you put forward in this review?

Through outlining the studies demonstrating the effect of tissue-specific factors on T cells, we stressed the importance of comprehensive understanding with careful examination to improve our current therapeutic strategies depending on the tissue-of-origin of cancers. Furthermore, to empower cell therapies such as CAR T cells or TCR T cells, we also need to consider characteristics of tissues, including composition of stromal cells and metabolic properties of cancers, more carefully.

*Microenvironment-driven metabolic adaptations guiding CD8+ T cell anti-tumor immunity - Jaeoh Park, Pei-Chun Hsueh, Zhiyu Li, Ping-Chih Ho.