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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Tuesday, January 21, 2025
Anniina Färkkilä, MD, PhD, of the University of Helsinki, and colleagues performed spatial and molecular characterization of high-grade serous ovarian cancer (HGSOC) treated with chemotherapy, since the adaptation of antitumor immunity to standard chemotherapy has not yet been identified. Published in Cancer Cell, the results of this trial suggest that myeloid-driven spatial T-cell exhaustion has the potential to reveal immunotherapeutic targets that may induce CD8-positive T-cell–mediated antitumor immunity in this patient population.
“These findings will help us figure out which treatments work best for which patients and when they should be given,” said Dr. Färkkilä in an institutional press release. “We hope this research will lead to clinical trials where patients are selected for new immunotherapy treatments based on specific biomarkers.”
The investigators collected 117 HGSOC samples from 75 patients who participated in the DECIDER (ClinicalTrials.gov identifier NCT04846933) and Oncosys-OVA (NCT06117384) trials. Samples were stained with validated antibodies and subsequently scanned with the RareCyte CyteFinder scanner. The European Society for Medical Oncology–European Society of Gynaecological Oncology (ESMO-ESGO) 2019 guidelines were used to triage patients to undergo neoadjuvant chemotherapy.
Networks of interconnected myeloid cells, also called myelonets, were observed to contribute to CD8-positive T-cell exhaustion after chemotherapy. This demonstrated that M1/M2 polarization at the tumor-stroma interface correlates with both CD8-positive T-cell exclusion and exhaustion, which contributes to a poor response to chemotherapy. Moreover, this demonstrates that CD8-positive T cells undergo an immunomodulatory “neighborhood switch” from tumor to myeloid interactions when treated with neoadjuvant chemotherapy.
Increasingly versatile immune cells that appeared to form spatiotemporally dynamic microcommunities were identified via single-cell and spatial analyses, noted the study authors. Further, prominent myeloid and T-cell interactions were identified via NECTIN2 and TIGIT—proteins that interact and play a role in the immune response to malignant transformation—that were induced by chemotherapy. Thus, the authors believe, these findings suggest that NECTIN2-TIGIT signaling may predict response to immune checkpoint blockade.
Disclosure: Dr. Färkkilä reported no conflicts of interest. For full disclosures of the other study authors, visit cell.com.
