Researchers at UT Southwestern Medical Center have identified a genetic mutation that enhances immune system responses, significantly slowing melanoma growth.

The study revealed that the gene H2-Aa, when mutated, prevents tumor growth, as mice lacking this gene exhibited no tumor growth after exposure to melanoma cells.

Mice lacking H2-Aa showed increased infiltration of dendritic cells and CD8 T cells in tumors, while regulatory T cells that inhibit immune activity were reduced.

Interestingly, the study found that eliminating H2-Aa specifically on dendritic cells was enough to replicate the tumor-suppressing effects seen in mutant mice.

H2-Aa plays a critical role in producing an immune protein that helps the immune system differentiate between self and non-self proteins.

Dr. Beutler emphasized that targeting the human version of H2-Aa with monoclonal antibodies could enhance cancer treatment outcomes, potentially improving responses to existing immunotherapies.

The researchers developed a monoclonal antibody against H2-Aa, which demonstrated significant anticancer effects, particularly when used in combination with checkpoint inhibitor drugs.

This research is especially significant given that approximately 50-67% of melanoma patients do not respond to checkpoint inhibitors, highlighting the potential for improved treatment responses.

The findings of this study, published in the Journal of Experimental Medicine, indicate a promising new therapeutic target for cancer treatment.

Dr. Hexin Shi, Assistant Professor, co-led the study alongside Dr. Bruce Beutler, a Nobel Prize laureate known for his contributions to immune response receptors.

To identify genes that confer tumor resistance, the researchers utilized a technique called automated meiotic mapping (AMM) to create mouse models with genetic mutations.