@article{01KSA3DBF6NKZM6P4HH5Z52VS3,
  abstract     = {{Background: Immune checkpoint blockade (ICB) has revolutionized cancer treatment, including gynecological cancers, yet durable responses are observed only in subsets of patients. To improve efficacy, ICB is increasingly combined with complementary approaches. Although tissue-based biomarkers provide valuable information, their invasiveness and inability to capture systemic immune changes limit their utility. Peripheral blood offers a noninvasive alternative, but immune cell profiling in advanced cervical cancer (CC) and endometrial (EC) patients receiving ICB-based therapy remain underexplored. Methods: This exploratory translational study of the PRIMMO clinical trial (https://clinicaltrials.gov/search?id=%22NCT03192059%22) analyzed blood-based immune profiles from advanced CC (n=19) and EC (n=24) patients treated with an ICB-based regimen. Peripheral blood was collected at inclusion (baseline), on-treatment (week 7), and post-treatment (week 26 or earlier (< week 26) in case of earlier disease progression). Immune cell subsets and selected systemic immune mediators were assessed by multicolor flow cytometry and ELISA. Results: At baseline, CTLA-4(+)PD-1(+)CD4(+) T cells and CD161(+)CD56(+)CD16(+) NK cells were associated with survival outcomes only, while the combined immune score was associated with both treatment response and survival outcomes. During treatment, responders exhibited relatively stable immune profiles at both early and late treatment time points. In contrast, non-responders showed sustained decreases in pDCs and increases in activation (CD69, CD137, HLA-DR) and co-stimulatory/inhibitory markers (CTLA-4, ICOS, Tim-3) across T cell subsets, including co-expression at both early and late phases of treatment. NK cell subsets also displayed increased activation features (CD69, CD161, HLA-DR). These changes were accompanied by expansion of immunoregulatory populations (MDSCs and Tregs), quantified based on phenotypic markers only, along with an increased kynurenine/tryptophan ratio, and elevated sPD-1 levels. Tumor-type-specific analyses suggested relatively more NK-related changes in CC and T cell-related changes in EC. Conclusion: Longitudinal immune changes, rather than baseline differences alone, distinguished responders from non-responders. Non-response to the combination treatment is not characterized by immune inactivity but rather associated with sustained and coordinated increases in both activation and regulatory immune features, suggesting a shift toward systemic immune imbalance following treatment. These findings support the need for longitudinal, integrative immune monitoring strategies in future clinical trials.}},
  articleno    = {{1794131}},
  author       = {{Baiden-Amissah, Regina Esi Mensimah and Tuyaerts, Sandra and Annibali, Daniela and Herreros-Pomares, Alejandro and De Wispelaere, Wout and Benedetto, Rossana Maria and De Jaeghere, Emiel and Van Nuffel, An M. T. and Vuylsteke, Peter and Henry, Stéphanie and Bich Trinh, Xuan and Van Dam, Peter A. and Aspeslagh, Sandrine and De Caluwé, Alex and Naert, Eline and Vandecasteele, Katrien and Denys, Hannelore and Amant, Frédéric}},
  issn         = {{1664-3224}},
  journal      = {{FRONTIERS IN IMMUNOLOGY}},
  keywords     = {{anti-PD-1 therapy,blood-based biomarkers,combination therapy,cyclophosphamide,drug repurposing,gynecological cancers,immune checkpoint blockade,radiotherapy,TUMOR,RESPONSES}},
  language     = {{eng}},
  pages        = {{16}},
  title        = {{Circulating immune cell profiling in advanced cervical and endometrial cancer patients treated with PD-1 blockade, radiotherapy, and immune modulation in the PRIMMO trial}},
  url          = {{http://doi.org/10.3389/fimmu.2026.1794131}},
  volume       = {{17}},
  year         = {{2026}},
}

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