KEY TAKEAWAYS
- The study aimed to compare immune TME in ICI-responders vs. non-responders in patients with MMRd endometrial cancer.
- The study highlighted immune TME features for identifying patients with MMRd EC having primary ICI resistance for novel immunotherapy trials.
Patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) benefit significantly from immune checkpoint inhibitors (ICI). However, understanding responses and identifying predictors of primary resistance remains incomplete.
Juan Francisco Grau Bejar and the team aimed to analyze the immune tumor microenvironment (TME) in MMRd EC, comparing responders and non-responders to ICI using spatial immune profiling and hierarchical clustering analysis.
The results revealed that non-responders (NRs) in the study exhibited significantly lower levels of CD8+ cells, absence of terminally differentiated T cells, lack of mature tertiary lymphoid structures and dendritic cells, and reduced expression of human leukocyte antigen class I. Despite this, no single marker could reliably predict response versus non-response to ICI.
Clustering analysis identified a set of four immune features that collectively predicted ICI response with 92% accuracy. Additionally, 80% of NRs lacked programmed death-ligand 1, while 60% expressed other actionable immune checkpoints (T-cell immunoglobulin and mucin domain-containing protein-3, indoleamine 2,3-dioxygenase 1, or lymphocyte activation gene 3).
The study’s findings highlighted the potential of immune TME features in identifying patients with MMRd EC and primary resistance to ICI. These patients may benefit from participation in trials exploring novel immunotherapeutic combinations.
Research was supported by the Comprehensive Program of Cancer Immunotherapy & Immunology I (CAIMI-I) at the Vall d’Hebron Institute of Oncology, funded by the BBVA Foundation. Additional support was provided by the Programme Parrainage Chercheur at Institut Gustave Roussy.
Source: https://pubmed.ncbi.nlm.nih.gov/38955419/
Grau Bejar JF, Yaniz Galende E, Zeng Q, et al. (2024). “Immune predictors of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.” J Immunother Cancer. 2024 Jul 1;12(7):e009143. doi: 10.1136/jitc-2024-009143. PMID: 38955419.
