Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma as a predictor for response and survival in patients treated with ipilimumab when progressing to stage IV
Stefan Diem1, Omar Hasan Ali2,6, Christoph Ackermann1, Viktor Koelzer3, Wolfram Jochum4, Daniel E. Speiser5, Burkhard Ludewig6, Kirsten Mertz3, Lukas Flatz2,6,7
1Department of Oncology, Kantonsspital St. Gallen; 2Department of Dermatology and Allergology, Kantonsspital St. Gallen; 3Department of Pathology, Kantonsspital Basel; 4Department of Pathology, Kantonsspital St. Gallen; 5Department of Oncology, University of Lausanne; 6Institute of Immunobiology, Kantonsspital St. Gallen; 7Department of Dermatology, University Hospital Zürich
Prognosis of metastatic melanoma significantly improved due to the introduction of checkpoint inhibitors. The role of tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma remains unclear.
We retrospectively analyzed tissue samples of primary melanomas and metastatic lymph nodes before treatment, for microenvironmental changes in association with objective responses and survival to treatment with ipilimumab.
4 out of 9 patients (44%) showed an objective response during treatment with ipilimumab (RECIST). Responders showed high PD-L1 expression by immune cells in the primary tumor but no specific pattern of inflammation. Strikingly, all responders exhibited high degrees of T cell infiltration in their lymph node metastases. Lymph node metastasis size did not correlate with the clinical responses. Mean time from diagnosis of stage III melanoma to development of stage IV melanoma was significantly different in responders vs. non-responders (36 months vs. 14 months).
We conclude that T cell infiltration in metastatic lymph nodes in stage III melanoma patients correlates with survival following treatment with ipilimumab. Possibly, T cell infiltration in lymph node metastases may correlate better with clinical outcome as compared to T cell infiltration in primary tumors, since the immune landscape in more advanced disease (e.g. in metastatic lymph nodes) may be more directly related to the immune biology of stage IV disease.