The study*, published in Science Immunology, was conducted by Dr David Barras, Dr Eleonora Ghisoni, Dr Johanna Chiffelle and colleagues and directed by Dr Denarda Dangaj and Pr George Coukos , members of the Lausanne Branch of the Ludwig Institute for Cancer Research. New findings from this research illuminate that individuals who respond positively to adoptive T cell therapy for metastatic melanoma demonstrate synchronized communication between myeloid cells within the tumor and tumor-reactive CD8+ T cells.
In the ongoing quest to improve outcomes for metastatic melanoma, researchers have turned to adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs). While showing promise for some patients, its long-term effectiveness remains limited. Seeking new insights to enhance TIL-ACT responses, this research illuminate that individuals who respond positively to adoptive T cell therapy for metastatic melanoma demonstrate synchronized communication between myeloid cells within the tumor and tumor-reactive CD8+ T cells. The team examined longitudinal samples from 13 metastatic melanoma patients treated with TIL-ACT, after progression on immune checkpoint blockade therapies, in a phase 1 clinical study at the CHUV.
Through detailed analyses of preand post-ACT tumor tissues, the researchers uncovered complex cellular interactions within the tumor microenvironment (TME). They identified robust intratumoral networks among tumor-reactive T and stimulatory myeloid populations in responsive patients. These networks were linked to distinct states of CD8+ TILs marked by heightened cytotoxicity and exhaustion, along with myeloid cells showing increased type I interferon signaling and co-stimulation.
Significantly, successful TIL-ACT therapy was found to reprogram the myeloid compartment and enhance TIL-myeloid networks, emphasizing their importance in melanoma treatment responses. The study’s systematic approach identified potential myeloid-T cell network-based biomarkers, offering promise for improved patient selection and guiding future ACT clinical trials.
This work is the result of a collaboration between the Department of Oncology, Dermatology, Pathology, Radiology, Nuclear Medicine, Visceral Surgery at the Centre Hospitalier Universitaire Vaudois (CHUV), the Swiss Institute of Bioinformatics and the Department of Pathology and Immunology, University of Geneva. Research in for this study was supported in part by the Swiss National Science Foundation, the Ludwig Institute for Cancer Research, R’Equip (to Dr Dangaj), the University of Lausanne, the Swiss Canton of Vaud, Bristol Meyers Squibb, and the following foundations: Biltema, Paul Matson and Cancera (to George Coukos).
* Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+ T-myeloid cell networks in melanoma