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Cancer Immunology, Immunotherapy

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Open Access 01-02-2024 | Melanoma | Research

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

Authors: J. M. Versluis, E. P. Hoefsmit, H. Shehwana, P. Dimitriadis, J. Sanders, A. Broeks, C. U. Blank

Published in: Cancer Immunology, Immunotherapy | Issue 2/2024

Abstract

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/mm² 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⁺/mm² 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.

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Title: Tumor characteristics of dissociated response to immune checkpoint inhibition in advanced melanoma
Authors: J. M. Versluis
E. P. Hoefsmit
H. Shehwana
P. Dimitriadis
J. Sanders
A. Broeks
C. U. Blank
Publication date: 01-02-2024
Publisher: Springer Berlin Heidelberg
Keywords: Melanoma
Melanoma
Published in: Cancer Immunology, Immunotherapy / Issue 2/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03581-6

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Abstract

Introduction

Methods

Results

Conclusion

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