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Activity of T Cells in Metastatic Melanoma Resistant to Immune Checkpoint Inhibitor Treatment


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In a study reported in the Annals of Oncology, Andersen et al found that tumor-infiltrating lymphocytes isolated from metastatic melanoma lesions in patients with disease progression after checkpoint inhibitor therapy remain functional. Moreover, they concluded these tumor-infiltrating lymphocytes from such patients may exhibit antitumor activity as part of immune therapy. Marco Donia, MD, PhD, of the Center for Cancer Immune Therapy, Herlev Hospital, Denmark, is the corresponding author of the Annals of Oncology article.

Marco Donia, MD, PhD

Marco Donia, MD, PhD

The study involved assessment of tumor-infiltrating lymphocytes from 23 metastases from individual patients. Metastases had progressed on or during anti–programmed cell death protein 1 (PD-1) therapy in all patients and anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) treatment in 17.

Assessment of tumor-specific immune responses with co-culture assays of tumor-infiltrating lymphocytes and autologous tumor cells showed that functional antitumor immune responses could be detected in 19 patients (83%). Autologous tumors were recognized by CD8-positive tumor-infiltrating lymphocytes in 18 patients (78%) and by CD4-positive tumor-infiltrating lymphocytes in 16 (70%). Tumor cells were recognized by a median of 23% of CD8-positive tumor-infiltrating lymphocytes (range = 1%–84%). Localization of intratumoral immune infiltrates was heterogeneous among the metastatic melanoma samples.

Trial of Autologous Tumor-Infiltrating Lymphocytes

In a phase I/II trial, 11 evaluable patients with metastatic melanoma resistant to checkpoint inhibitor therapy were treated with autologous tumor-infiltrating lymphocytes, lymphodepleting chemotherapy, peg-interferon-α2b, and interleukin-2. Partial responses were observed in two patients, with stable disease observed in eight patients.

The investigators concluded, “Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients [for whom previous checkpoint inhibitor treatment failed]. These patients can still respond to an infusion of unselected autologous [tumor-infiltrating lymphocytes]. Our results warrant further testing of novel immune reactivation strategies in melanoma patients [in whom multiple checkpoint inhibitor therapy has failed].”

The study was supported by The Danish Cancer Society, Aase and Einar Danielsen Foundation, The Beckett Foundation, Herlev and Gentofte Hospital Research Council, and The Danish Council for Independent Research. ■

Andersen R, et al: Ann Oncol 29:1575-1581, 2018.


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