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Rare Immune Cell May Predict Immunotherapy Response in Melanoma

News
Article

Vd1-gd T cells, a rare type of immune cell, have been found to potentially predict how likely it is that certain patients with advanced skin cancer will be responsive to treatment via immunotherapy, according to recently published research.

Melanoma pathology: vertical growth phase

Image courtesy of DermNet

Melanoma pathology: vertical growth phase

Image courtesy of DermNet

A rare type of immune cell has been found to potentially predict how likely it is that certain patients with skin cancer will be responsive to treatment via immunotherapy, according to recently published research.

A team of British researchers from King’s College London, Guy’s and St Thomas’ Hospital Trust, and the Francis Crick Institute, who reported their findings in a study published in the journal Nature Cancer, found that Vd1-gd T cells had the ability to recognize and kill cancer cells without identifying mutations, and can be found inside tumors where the immune checkpoint protein programmed cell death protein 1 (PD-1) is also present, as explained in a news release issued by King’s College London.

“The study findings may help doctors decide which patients are most likely to benefit from current immunotherapies,” stated co-first author Dr. Shraddha Kamdar, a Research Fellow at King’s College London, in the news release. “These therapies are both costly and importantly can cause severe and life-long side effects, so it is important to be able to predict when they will actually work.”

“Our study highlights the importance of understanding the contributions of lesser-studied immune cell types in efforts to improve the effectiveness immunotherapies,” added co-first author and PhD student Daniel Davies in the release.

The findings were based on clinical trial data of 127 patients with melanoma who had been treated with PD-1-targeting immune checkpoint inhibitors, and this data revealed that Vd1-gd T cells’ presence could predict positive response to immunotherapy, especially in cancers with a low number of mutations, according to the news release. Researchers then grew cells from human tissue in a laboratory setting to illustrate that immune checkpoint inhibition therapy could reactivate Vd1-gd T cells, and learned that therapies utilizing Vd1-gd T cells could be effective for relatively longer than therapies using other types of T cells.

Immune checkpoints, a standard element of a patient’s immune system, the body from destroying healthy cells and engage when proteins on the surface of T cells identify and bind to immune checkpoint proteins on cells such as tumor cells, and the bond between the checkpoint and the protein deactivates T cells, as explained by the National Cancer Institute, which also said on its website that immune checkpoint inhibitors block the binding of checkpoint and partner proteins, enabling the T cell to remain active and fight cancer cells.

“Many of these immune checkpoints are best considered as sort of molecular brakes on the immune system that keep the immune system from getting too activated,” Dr. Jedd D. Wolchok, director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York, told CURE® last year.

Given the potential side effects associated with immunotherapy, being able to predict which patients are likely to benefit from the treatment could be useful information for patients and their care teams.

“In the case of immunotherapy, the side effects really resemble autoimmune disease, so inflammation of normal organs, because really, what we've let the immune system do with these immune checkpoint inhibitors is to run past that physiologic governance, run past that ceiling of activity that normally keeps our immune system under control,” Wolchok said.

“We see inflammation of the skin, or rash. We see inflammation of the intestines, which is diarrhea or upper gastrointestinal upset. We can see inflammation of the liver, which is manifested usually on blood tests, where we see liver function tests becoming abnormal. We see fatigue that happens with these drugs. Sometimes that's due to immune attack of normal glands that produce hormones in the body, like the thyroid or the pituitary gland. Those are really some of the more common ones. But really, what we've seen is inflammation in almost every part of the body. We've seen kidney inflammation, we've seen heart, lung, brain inflammation.”

Reference

Davies D, Kamdar S, Woolf R, et al. PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy. Nat Cancer (2024). https://doi.org/10.1038/s43018-023-00690-0

[This article was originally published by our sister brand, Cure.]

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