CD4+ T cells, or helper T cells, are one type of lymphocyte that helps coordinate the immune response against infection and disease. The cells are crucial in achieving a regulated effective immune response to pathogens. They carry out multiple functions ranging from activation of B-lymphocytes, cytotoxic T cells, as well as nonimmune cells. Now, researchers led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) reveal unprecedented insights into CD4+T cells which show promise for immunotherapies against melanoma.

Their findings are published in Science Immunology in an article titled, “CD4+ T cell immunity against cutaneous melanoma encompasses multifaceted responses,” and reveal CD4+ T cells are effective in controlling melanoma.

University of Melbourne’s Emma Bawden, PhD, a 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.

For decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor.

Melanoma treatment depends on the stage of a patient’s melanoma and their overall health. During its early stages, melanoma can be successfully treated with surgery alone. Other types of cancer treatment such as immunotherapy may be effective for more advanced stages of melanoma.

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

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

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, MD, PhD, who is also a 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 Gebhardt.

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