Tumor characteristics of dissociated response to immune checkpoint inhibition in advanced melanoma.

Autor: Versluis JM; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Hoefsmit EP; Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Shehwana H; Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Dimitriadis P; Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Sanders J; Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Broeks A; Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands., Blank CU; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. c.blank@nki.nl.; Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. c.blank@nki.nl.; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands. c.blank@nki.nl.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Jan 27; Vol. 73 (2), pp. 28. Date of Electronic Publication: 2024 Jan 27.
DOI: 10.1007/s00262-023-03581-6
Abstrakt: Introduction: Immune checkpoint inhibition (ICI) has improved patients' outcomes in advanced melanoma, often resulting in durable response. However, not all patients have durable responses and the patients with dissociated response are a valuable subgroup to identify mechanisms of ICI resistance.
Methods: Stage IV melanoma patients treated with ICI and dissociated response were retrospectively screened for available samples containing sufficient tumor at least at two time-points. Included were one patient with metachronous regressive and progressive lesions at the same site, two patients with regressive and novel lesion at different sites, and three patients with regressive and progressive lesions at different sites. In addition, four patients with acquired resistant tumor samples without a matched second sample were included.
Results: In the majority of patients, the progressive tumor lesion contained higher CD8 + T cell counts/mm 2 and interferon-gamma (IFNγ) signature level, but similar tumor PD-L1 expression. The tumor mutational burden levels were in 2 out 3 lesions higher compared to the corresponding regressive tumors lesion. In the acquired tumor lesions, high CD8 + /mm 2 and relatively high IFNγ signature levels were observed. In one patient in both the B2M and PTEN gene a stop gaining mutation and in another patient a pathogenic POLE mutation were found.
Conclusion: Intrapatient comparison of progressive versus regressive lesions indicates no defect in tumor T cell infiltration, and in general no tumor immune exclusion were observed.
(© 2024. The Author(s).)
Databáze: MEDLINE
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