Credit: Kathryn T. Iacono
Research in mice has revealed a potential approach to cancer treatment—a way to inhibit the recruitment of regulatory T cells (Tregs) to tumors.
The study showed that dendritic-cell-derived interleukin-27 (IL-27) promotes Treg recruitment in models of lymphoma, melanoma, and fibrosarcoma.
This suggests that if cancer therapies can inhibit IL-27’s immunosuppressive function, they could more effectively activate other T cells to attack and destroy tumors.
Researchers described this discovery in the Journal of Leukocyte Biology.
“Our study not only provides a new insight into the effects of interleukin-27 in regulatory T-cell biology but also greatly improves our understanding of the physiological functions of interleukin-27, especially in tumor immunology,” said study author Siyuan Xia, of Nankai University in Tianjin, China.
“We hope our study could shed new light on developing novel interventional therapies by targeting regulatory T cells in cancer patients.”
The researchers made their discovery by using mice deficient in a specific subunit of IL-27 called p28. They compared tumor-infiltrating lymphocytes between IL-27p28 knockout mice and wild-type mice.
This revealed that Tregs were significantly decreased in knockout mice transplanted with EL-4 lymphoma, B16 melanoma, and MCA-induced fibrosarcoma.
The team also found that IL-27 promotes the expression of CCL22, which is known to mediate Treg recruitment to tumors. And tumor-associated dendritic cells were the major source of CCL22.
When the researchers restored CCL22 or IL-27 in the knockout mice, they observed significant restoration of the tumor-infiltrating Tregs.
Furthermore, tumor-infiltrating CD4 T cells produced much more IFN-γ in the IL-27p28 knockout mice than in wild-type mice. According to the researchers, this reinforces the physiological importance of Tregs in suppressing an antitumor immune response.
“Suppressive and regulatory pathways in the immune system are incredibly important for normal health and preventing autoimmunity,” said John Wherry, PhD, Deputy Editor of the Journal of Leukocyte Biology.
“However, these pathways also get exploited by cancer to prevent immune responses leading to cancer progression. The current studies point to an important regulatory network centered on interleukin-27 that could be targeted to improve immunity to cancer in humans.”
