Regional Lymph Nodes Guarded by Immune Cells

NEW YORK (Reuters Health) – Instead of traveling between lymph nodes and the blood stream, a newly discovered population of long-lived T cells stays in regional lymph nodes and guards against cancer, researchers report.

“A population of tumor-specific T cells, named resident memory T cells (Trm cells), persists in tumor-draining lymph nodes where they protect against melanoma,” co-senior author Dr. Chao Cheng of Baylor College of Medicine in Houston, Texas, told Reuters Health by email.

“Because immune cells constantly recirculate through lymph nodes, we were surprised to find that T cells stably reside in lymph nodes to fight cancer,” co-senior author Dr. Mary Jo Turk of the Geisel School of Medicine at Dartmouth, in Lebanon, New Hampshire, added by email.

As reported in Immunity, the two researchers and their colleagues investigated the role of Trm cells and circulating memory (Tcirm) cells in anti-tumor responses in lymph nodes.

They used sequencing techniques to determine the unique transcriptional profile that makes resident T cells specific to lymph nodes and to cancer. They found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy, with Trm cells dominating lymph nodes. Single-cell RNA-sequencing profiles of Trm cells in lymph nodes and skin were distinct, and T cell clonotypes that occupied both tissues were predominantly maintained as Trm cells in lymph nodes.

Using computational analysis of melanoma-specimen data from The Cancer Genome Atlas, the researchers found that the presence of T cells with this gene signature predicted better outcomes and improved survival for human melanoma patients with lymph node metastases.

“These studies reveal a new population of T cells that is vital for counteracting the earliest stages of cancer metastasis,” Dr. Turk said in a press release.

Trm cells provided long-term protection against melanoma seeding in lymph nodes. Expanded Trm populations were present in melanoma-involved lymph nodes from patients, and their transcriptional signature predicted better survival in melanoma patients. Tumor-specific Trm cells persisted in lymph nodes, protected against tumor seeding and restricted metastatic cancer.

“In some melanoma patients, melanoma metastasizes to lymph nodes, while in other patients this does not occur,” Dr. Cheng said. “This study may provide critical new insight to understanding immune resistance against metastasis.”

Dr. Christiane Querfeld, an associate professor of dermatology and dermatopathology, and the director of the Cutaneous Lymphoma Program at City of Hope Comprehensive Cancer in Duarte, California, said, “The study reveals that both tumor location and tissue define the optimal features of a protective memory T cell response on a transcriptional (gene) level. The study also shows that long-lasting residing (resident memory) T cells in lymph nodes are critical mediators of an antitumor response preventing spread in melanoma.”

“Tumor-infiltrating lymphocytes frequently display an exhausted phenotype (upregulation of exhaustion markers/checkpoint markers) that is orchestrated by the tumor microenvironment,” she told Reuters Health by email. “While immunotherapies are effective and have transformed treatment approaches in cancer, challenges remain to induce long-term antitumor responses by generating tumor-infiltrating lymphocytes to effectively target the tumor cells.”

“Resident memory T cells – characterized by expression of CD103, CD69 with absence or low CD62L – are a subset of a long-lasting T cell population, and the development of immunotherapeutic strategies focusing on resident memory T cells (Trm) could be critical not only in controlling tumor growth but also, as the study shows, in preventing tumor recurrences,” noted Dr. Querfeld, who was not involved in the study.

Dr. Turk noted that “new therapeutic strategies might be developed to improve cancer treatment by manipulating or enhancing Trm cell populations in lymph nodes.”

“We still don’t know what types of immunotherapy can generate these protective Trm cells,” she said. “We also don’t know if lymph node Trm cells can be generated for cancers other than melanoma.”

“We are moving our research forward to understand how resident memory T cells could be positioned throughout tissues to efficiently limit cancer spreading,” Dr. Turk added.

The study did not receive commercial support. The authors and Dr. Querfeld declare no competing interests.

SOURCE: Immunity, online September 14, 2021.

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