Researchers have discovered that the use of antibody blocks TREM2 proteins can empower immune cells and destroy tumors, and eliminate completely in mouse models when they were combined with anti-PD-1 immunotherapy.
Anti-cancer immunotherapy uses the body’s immune system to destroy tumor cells. Despite breakthroughs in this medical arena, a limited number of patients actually benefit from these therapies. A significant reason for the less-than-desirable responses is tumor cells’ ability to circumvent various T-cell immune mechanisms. Therefore, populations of resistant tumor cells hinder the effectiveness of current immunotherapeutic approaches in many patients.
New research to address this has uncovered a promising means to overcome tumor cell resistance to T-cell immunity. The finding is based on a protein, TREM2, expressed in various types of myeloid cells such as macrophages, dendritic cells, and granulocytes. TREM2 is found to be expressed in tumor-associated macrophages. It may be targeted to stunt tumor growth and improve immunotherapies’ outcomes, including checkpoint inhibitor therapy aimed at enhancing T cell immune function against cancer cells.
Results of a recent study showed that TREM2 deficient mice are more resistant to cancer growth and more responsive to anti-PD-1 (checkpoint inhibitor) immunotherapy than wild-type mice. Also revealing was that when treating wild-type mice with an anti-TREM2 monoclonal antibody, tumor growth was impeded, and regression was observed with anti-PD-1 co-treatment. Both scenarios were associated with the expansion of myeloid cell subsets expressing molecules that enhance T cell responses.
Analysis of cancer cases showed that TREM2 was expressed in tumor macrophages in over 200 human cancer cases. Increased survival was associated with lower TREM2 expression in at least two cancer types. Taken together, the research study results show that TREM2 deficiency and anti-TREM2 antibody treatment both adversely affect tumor growth in mice and that blocking TREM2 expression changes the tumor macrophage environment. When TREM2 is absent or blocked with antibody, anti-PD-1 treatment yields improved T-cell responses against cancer cells. Targeting TREM2 may improve clinical outcomes of checkpoint inhibitor therapy and increase survival for more patients with cancer.
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Achilles Heel of Immunotherapy-Resistant Cancers Revealed – and Eliminated – in Early Studies | BioSpace. (2020). Retrieved 31 August 2020, from https://www.biospace.com/article/achilles-heel-of-immunotherapy-resistant-cancers-revealed-and-eliminated-in-early-studies-/