Tumor immune cell patterns predict melanoma immunotherapy response

The findings, published in Cancer Discovery, a journal of the American Association for Cancer Research, show that patients whose tumors contained active networks of cancer-killing T cells were more likely to benefit from treatment, while those with dense clusters of plasma cells were far less likely to benefit.

Why it matters 

What the study did

To address this question, researchers analyzed tumor biopsies from patients enrolled in the SWOG S1616 clinical trial. All had melanoma that had already progressed on anti-PD-1 therapy. Patients were randomly assigned to receive either a combination of two immunotherapies - ipilimumab (which targets CTLA-4) and nivolumab (which targets PD-1) - or ipilimumab alone. Tumor biopsies were taken before treatment and again about a month later. Working with collaborators at the Parker Institute for Cancer Immunotherapy and industry partners, the team combined genetic sequencing with high-resolution imaging to map not just which genes were active in the tumors, but where different immune and cancer cells were physically located.

What they found

The researchers found that tumor genetics alone did not explain which patients responded to treatment. Instead, the most important differences were seen in the tumor's immune environment.

Rather than acting in isolation, immune and cancer cells formed organized patterns of interaction, often referred to as cellular neighborhoods, where different cell types work together within specific regions of the tumor. In contrast, tumors that did not respond to treatment often contained dense clusters of plasma cells. These plasma cell-rich regions were associated with reduced T cell activity and continued tumor growth, suggesting they may be linked to a tumor environment that is less able to support an effective immune attack.

The study also highlights why the physical location of immune cells inside a tumor is so important. The researchers found that T cells in responding tumors were positioned near blood vessels and other supportive immune cells, allowing them to move into the tumor and coordinate an effective attack.

What this means for patients

The findings suggest it may eventually be possible to use tumor structure, not just genetics, to help guide treatment decisions in melanoma, identifying patients most likely to benefit from combination immunotherapy and those who may need a different treatment approach sooner.

What's next

Researchers say the next step is figuring out how to reshape the tumor environment in patients whose cancers resist immune attack, and how to better combine immunotherapy with treatments such as targeted therapy, chemotherapy or radiation to improve response rates.

Source:

University of California - Los Angeles Health Sciences

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