Activity of T Cells From Patients With Metastatic Melanoma Resistant to Immune Checkpoint Inhibitor Treatment

Key Points

  • Tumor-infiltrating lymphocytes from checkpoint inhibitor–resistant metastatic lesions recognized and were active against autologous tumor.
  • Evidence of activity of immune therapy with unselected autologous tumor-infiltrating lymphocytes was observed in checkpoint inhibitor–resistant patients. 

In a study reported in 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 can exhibit antitumor activity as part of immune therapy.

Function of T Cells

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–CTLA-4 treatment in 17.

Assessment of tumor-specific immune responses with coculture 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 2 patients, with stable disease observed in 8.

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.

Marco Donia, MD, PhD, of the Center for Cancer Immune Therapy, Herlev Hospital, Denmark, is the corresponding author for the Annals of Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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