Immune Cells in Sentinel Nodes May Predict Melanoma Progression

Lymph node with almost complete replacement by metastatic melanoma; source: ‎Gabriel Caponetti, MD.

Melanoma patients who had CD30-positive T cells present in their sentinel lymph nodes were more likely to have disease progression compared with patients whose node biopsies were negative for these immune cells, according to the results of a small study published recently in Cancer Research.

According to study author Monica Rodolfo, PhD, staff scientist in the Immunotherapy Unit at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, this study provides evidence that “the immune system is crucially involved in controlling tumor growth and that sentinel nodes are endowed with precise information on cancer behavior.”

Current standard of care for patients with melanoma is to undergo sentinel lymph node biopsy for the staging and management of their disease. When biopsies show tumor-positive sentinel lymph nodes, patients undergo regional lymphadenectomy and are subclassified according to several predictive independent prognostic factors.

Rodolfo and colleagues sought to identify a more precise way to subclassify melanoma patients in order to better guide adjuvant treatment.

“Because of its proximity to the tumor, the sentinel node could contain early information about the developing cancer and its interaction with the immune system,” Rodolfo told Cancer Network.

The researchers analyzed the transcriptional profiles of archival specimens taken from sentinel node biopsies of 42 patients with melanoma at different stages of disease progression. Samples from patients who had positive nodes were further analyzed for lymphocytes and results were compared among patients whose tumor had recurred or not recurred at 5 years post-surgical removal of the primary tumor.

Results showed that sentinel lymph nodes of patients whose melanoma recurred after 5 years had an impaired microenvironment with dysregulated genes that were involved in processes such as cell survival, cell proliferation, and metabolism. Gene expression profiles showed that patients with progressing disease had upregulation of the TNF receptor family member CD30/TNFRSF8. Progressing patients were found to have higher numbers of CD30-positive lymphocytes in their node biopsies.

“CD30 expression seemed to encompass a panel of T cells mostly exhibiting tolerogenic or exhausted features, thus representing a potential marker of an immune system that is ‘permissive’ to tumor dissemination in the draining lymph nodes,” the researchers wrote.

To determine if CD30-positive cells could be detected in peripheral blood, the researchers also collected blood samples from 25 patients with stage III and stage IV melanoma and compared them with blood collected from age- and gender-matched healthy donors. Melanoma patients had significantly increased CD30-positive lymphocytes compared with the healthy patients, “indicating a systemic accumulation of CD30-positive lymphocytes,” according to the researchers.

“Our study points to the study of genetic signatures as a tool to gain information about the interactions occurring between cancer cells and the immune system, and their potential implications in disease outcome,” Rodolfo said. “In addition, we hypothesize that CD30 may become a novel target for treatments aimed at restoring effective antitumor immune responses in melanoma patients.”