Helper immune cells become killers to control melanoma

New Australian research has revealed a type on immune cell called CD4+ T cells traditionally thought to only assist other immune cells are effective in controlling melanoma.

The new findings challenge the conventional understanding of these ‘helper’ T cells in cancer immunity and indicate they may show potential for future immunotherapies against the disease.

It’s estimated more than 18,200 Australians were diagnosed with melanoma in 2023. It is the most aggressive form of skin cancer.

“Our in-depth study, using animal models, unravelled the complex biology of CD4+ T cells in melanoma and how they control cancer,” says Emma Bawden, a postdoctoral researcher at the Doherty Institute in Australia, and lead author of a study in Science Immunology.

“Using microscopic live imaging, we visualised the activities and interactions of CD4+ T cells with other cell types in the tumour microenvironment. Our findings challenge previous assumptions by showing that CD4+ T cells can combat tumours through a multitude of pathways.”

Usually these helper T cells aid the CD8+ T cells (also known as cytotoxic or ‘killer’ T cells) that eliminate cancer cells.

Melanoma-specific CD4+ T cells (green) surrounding partially destroyed melanoma cells (red) in the skin. Credit: Dr Emma Bawden and Teagan Wagner

But the research team found, in mice, host cells surrounding melanoma that expressed a molecule known as MHCII triggered helper T cells to become killers themselves. Helper cells could also harness other pathways to kill cancer cells.

Thomas Gebhardt, a senior research fellow at the Doherty Institute, adds understanding helper T cell responses could pave the way for more effective immunotherapies against melanoma.

“While CD4+ T cells are often viewed as accessory cells regulating the function of other immune cells, our work shows they can work effectively on their own,” says Gebhardt, who is senior author of the study.

“Therefore, harnessing their potential therapeutically holds great promise for the development and improvement of current cancer immunotherapies.”

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