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Predicting Immunotherapy Responsiveness Based on T-Cell Expression in Patients With Advanced Skin Cancer

By: Joshua D. Madera, MD
Posted: Thursday, February 1, 2024

Responsiveness to immunotherapy may be more easily predicted in patients with advanced skin cancer by using a rare subset of T cells called V-delta 1 gamma-delta (Vd1-gd) T cells, according to a study published in Nature Cancer. These findings may launch additional investigative efforts focused on establishing efficacious treatment alternatives for this patient population, suggested Shraddha Kamdar, PhD, of King’s College London, and colleagues.

“The study findings may help [physicians] decide which patients are most likely to benefit from current immunotherapies. These therapies are both costly and importantly can cause severe and lifelong side effects, so it is important to be able to predict when they will actually work,” explained Dr. Kamdar in a King’s College London press release.

A total of 127 patients with advanced melanoma were recruited for the study. All patients had previously received treatment with anti–PD-1 or anti–PD-L1 inhibitors. Skin samples from the breast or abdomen were obtained from all patients before they underwent elective plastic and reconstructive surgical procedures. Tissue samples were subjected to various biochemical assays to quantify protein expression.

The study findings showed that an increased expression of Vd1-gd T cells was significantly associated with a positive response to therapeutic intervention with immune checkpoint inhibitors. These responses were more pronounced when the tumors had a reduced number of mutations. In addition, Vd1-gd T cells grown from human tissues were successfully able to be reactivated by immune checkpoint inhibitor therapies. Moreover, resistance to suppression from cancer cells was more evident in Vd1-gd T cells compared with common T cells.

Disclosure: For full disclosures of the study authors, visit nature.com.


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