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20 Jan 2024

The secret life of CD4+ T cells: from helpers to melanoma fighters

Researchers have revealed unprecedented insights into CD4+ T cells, a type of immune cell, which show promise for immunotherapies against melanoma, the most severe form of skin cancer.

In the study led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and published in Science Immunology, the researchers found that CD4+ T cells, traditionally called ‘helper T cells’ for their role in aiding the activation of other immune cells, are remarkably effective in controlling melanoma.

University of Melbourne’s Dr Emma Bawden, Postdoctoral Researcher at the Doherty Institute and lead author of the study, said this discovery challenges the conventional understanding of the role of CD4+ T cells in cancer immunity.

“Our in-depth study, using animal models, unravelled the complex biology of CD4+ T cells in melanoma and how they control cancer,” explained Dr Bawden.

“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.”

CD4+ T cells (green) attacking melanoma cells (red) in the skin. Time stamp represents h:min:s

The detailed analysis revealed the genetic makeup, developmental states and functions of CD4+ T cells in melanoma, showing the potential of harnessing CD4+ T cells for future therapies against the skin cancer.

University of Melbourne Professor Thomas Gebhardt, Senior Research Fellow at the Doherty Institute and senior author of the study, said that understanding CD4+ 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. Therefore, harnessing their potential therapeutically holds great promise for the development and improvement of current cancer immunotherapies,” said Professor Gebhardt.

More than 15,000 Australians are diagnosed with melanoma every year, a rare but highly aggressive form of skin cancer.

Peer review: Bawden E, et al. CD4+ T cell immunity against cutaneous melanoma encompasses multifaceted responses. Science Immunology (2024). DOI:

Collaboration: The researchers acknowledge that this work is the result of a collaboration between the Doherty Institute, the University of Bonn, the University of Sydney, the University of Melbourne, the Royal Prince Alfred Hospital, NSW Health Pathology, University of Maryland, the United States Department of Veterans Affairs, College Park, Marlene and Stewart Greenebaum Cancer Center, Peter MacCallum Cancer Centre, Telethon Kids Institute and the University of Western Australia.

Funding: This research was supported by the National Health and Medical Research Council (NHMRC), Australia; Cancer Council Victoria, Australia; German Research Council, Germany; University of Melbourne, Australia; Deutsche Forschungsgemeinschaft (DFG; German Research Foundation), Germany; Cancer Council Western Australia, Australia; Peter MacCallum Cancer Foundation, Australia; University of Sydney, Australia; McMurtrie Cancer Pathology Fellowship, Australia; Melanoma Institute Australia, Australia; Cancer Institute NSW, Australia;  Ainsworth Foundation, USA, The CLEARbridge Foundation, Australia; and the Cameron Family.