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Publications of the Week

Extricating Human Tumor Immune Alterations from Tissue Inflammation

By May 16, 2022No Comments

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This week we profile a recent publication in Nature from first authors Florian Mair (pictured, left) and Jami Erickson (center) and the laboratory of Martin Prlic (right) at Fred Hutch and UW.

Can you provide a brief overview of your lab’s current research focus?

We study how tissue microenvironments and cell-cell interactions shape innate and adaptive immune responses in the context of inflammation, infection, and cancer. As an overarching lab goal and strategy, we strive to understand which signals control immune cell function and responses in these human tissues, so we can learn how to manipulate these signals for therapeutic purposes.

What is the significance of the findings in this publication?

Immunotherapies to treat solid tumors have achieved some spectacular successes, but major drawbacks persist, including severe toxicities and the inability to predict responsive vs. non-responsive patients. Ideally, immunotherapies would target a tumor-unique immune subset or interaction to minimize toxic off-target effects. Whether human tumor-unique immune subsets or interactions even exist was unclear due to a lack of data on how tumor-driven inflammation relates to general inflammatory processes in human tissues. In this study, we compared human tumor tissues to non-malignant, inflamed tissues. We observed extensive phenotypic and functional overlap in regards to the immune infiltrate, but we also identified a human tumor-unique regulatory T cell population. We report that this intratumoral Treg population is highly suppressive and can be distinguished from all other hematopoietic cells (in blood and tumor!) by the expression of just 2 surface proteins (IL-1R1 and ICOS). Overall, our study provides both a highly sought-after, human tumor-specific therapeutic target as well as novel insight for disentangling tumor-mediated immune changes from general inflammation-mediated immune changes.

What are the next steps for this research?

We are currently working on developing a bispecific antibody to therapeutically target these intratumoral regulatory T cells.

If you’d like us to mention your funding sources, please list them.

Emerson Collective, WRF, and NIH.

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