Immune predictors of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.
J Immunother Cancer
; 12(7)2024 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-38955419
ABSTRACT
BACKGROUND:
Patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) can derive great benefit from immune checkpoint inhibitors (ICI). However not all responses and predictors of primary resistance are lacking.METHODS:
We compared the immune tumor microenvironment of MMRd EC ICI-responders (Rs) and ICI non-responders (NRs), using spatial multiplexed immune profiling and unsupervised hierarchical clustering analysis.RESULTS:
Overall, NRs exhibited drastically lower CD8+, absent terminally differentiated T cells, lack of mature tertiary lymphoid structures and dendritic cells, as well as loss of human leukocyte antigen class I. However, no single marker could predict R versus NR with confidence. Clustering analysis identified a combination of four immune features that demonstrated that accurately predicted ICI response, with a discriminative power of 92%. Finally, 80% of NRs lacked programmed death-ligand 1, however, 60% exhibited another actionable immune checkpoint (T-cell immunoglobulin and mucin containing protein-3, indoleamine 2,3-dioxygenase 1, or lymphocyte activation gene 3).CONCLUSIONS:
These findings underscore the potential of immune tumor microenvironment features for identifying patients with MMRd EC and primary resistance to ICI who should be oriented towards trials testing novel immunotherapeutic combinations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
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Reparo de Erro de Pareamento de DNA
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Inibidores de Checkpoint Imunológico
Limite:
Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
J Immunother Cancer
Ano de publicação:
2024
Tipo de documento:
Article