Single-cell tumor microenvironment analysis sheds light on the results of metastatic melanoma

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There are several treatment options available for patients with advanced melanoma. Although these therapies have greatly improved patients ’prognosis, each person may respond to treatments differently. Treatment of melanomas that have spread to the central nervous system is especially difficult. In a new article published in Cancer clinical researchResearchers at the Moffitt Cancer Center reveal how different therapies affect the surrounding immune environment of metastatic melanoma tumors by location and identify a rare population of immune cells that is associated with better overall survival.

Different types of cancer tend to spread to specific places throughout the body. The common sites of melanoma metastases are the brain, lungs, liver, and bones. Approximately between 40% and 60% of they develop metastatic diseases in the central nervous system, while 5% of patients develop metastatic diseases in the area of ​​the leptomeninges, the two innermost layers of tissue that cover the brain and spinal cord, and the cerebrospinal fluid. Patients with leptomeningeal melanoma metastases have a very poor prognosis, with an average survival of only eight to ten weeks. Despite this , a handful of patients with leptomeningeal melanoma metastases show increased survival, but the reasons for this are unclear.

“In general, we know very little about tumors at this site or why they prove to be so deadly. We hope that these ideas will lead to the development of new therapies, with the ultimate goal of improving the clinical outcomes of patients with leptomeningeal melanoma metastases.” said Inna Smalley, Ph.D., first author of this study and assistant member of the Department of Cancer Physiology.

Moffitt researchers want to improve their understanding of why some patients with metastatic melanoma respond better than others and determine which cellular factors contribute to these enhanced responses at different metastatic sites. RNA expression patterns of individual melanoma and of 26 patients with metastatic melanoma of the skin, brain, and leptomeninges / cerebrospinal fluid, and used this information to determine the specific immune cell types present in each sample. They found that cell types in the tumor microenvironment varied according to the site of metastasis. Leptomeningngeal melanoma metastases were characterized by a suppressed immune environment, with a high percentage of dysfunctional CD4 and CD8 T cells that are unable to generate an immune response, and low levels of B cells. brain and skin metastases were much more similar in their immune environment, with enrichment for activated CD4 T cells.

The researchers looked at how the immune environment of metastatic sites is modulated by different regimens and what types of immune cells are associated with better responses. They compared data from one patient with leptomeningeal melanoma metastasis who had a good response to treatment and survived for more than 38 months, to data from five patients who had poor responses to treatment. They found that the long-term survivor had an immune environment that more closely resembled patients without leptomeningeal disease, while patients with a poor response had immune environments characterized by immunosuppressive myeloid cells and depleted lymphocytes, a recipe for decreased responses. antitumor. Samples derived after treatment revealed that the long-term survivor had cells characteristic of an active immune response and patients who responded poorly to therapy did not have these cells present.

An additional analysis of the dendritic that play an important role in the response to therapy showed that a subpopulation, called DC3, was associated with improved overall survival and the presence of an active T cell. , regardless of the of metastasis or history of treatment. The researchers confirmed the importance of DC3s for patient outcomes through preclinical studies in mouse models.

“Our study provides the first insights into the immune microenvironment of patients with leptomeningia metastasis and helps clarify why these individuals do so badly, “said Keiran Smalley, Ph.D., director of Donald A. Adam’s Center for Melanoma and Skin Cancer Excellence at Moffitt.” The tissue microenvironments of the metastatic sites of the brain and leptomeningia are very different and show differential responses to systemic therapy. ”


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More information:
Inna Smalley et al, Single-cell characterization of the immune microenvironment of cerebral melanoma and leptomeningeal metastases, Cancer clinical research (2021). DOI: 10.1158 / 1078-0432.CCR-21-1694

Citation: Single-cell tumor microenvironment analysis sheds light on the results of metastatic melanoma (2021, June 3) retrieved June 3, 2021 from https://medicalxpress.com/news/2021-06 -tumor-microenvironment-cell-metastatic-melanoma.html

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