Blood immunomap for prediction of responses to anti-PD-1 immunotherapy in metastatic non-small cell lung cancer
The identification of circulating predictors of response to ICB therapy is vital as very few of them meet the demands of the clinic. Herein, by using high-dimensionality mass cytometry, we designed a blood immunomap in metastatic NSCLC individuals who underwent anti-PD-1 treatment. We identified heightened frequencies of CD8<sup>+</sup>PD-L1<sup>+</sup> T cells in non-responders compared to responders. Notably, imaging mass cytometry data revealed that CD8<sup>+</sup>PD-L1<sup>+</sup> T cells were enriched in tumor biopsies, pleural infusions, and BAL of early-stage NSCLC individuals, proposing this cells subset as candidate not only for the advanced but also for early disease detection. Transcriptomic analysis unveiled that CD8<sup>+</sup>PD-L1<sup>+</sup> T cells displayed an exhausted phenotype related to their increased frequencies to non-responders to immunotherapy, and gene signatures correlated with the overall survival of an independent cohort. Overall, our study pinpoints immune-related events which may benefit the quest for detection of predictive biomarkers of immunotherapy responses.
Authors
- Ioannis Morianos (ORCID: https://orcid.org/0000-0001-5207-0869)
- Panagiota Stamou (ORCID: https://orcid.org/0009-0002-4628-8719)
- Sara De Biasi (ORCID: https://orcid.org/0000-0002-3217-9821)
- Charalampos Fotsitzoudis
- Konstantina Dede
- Panayotis Verginis (ORCID: https://orcid.org/0000-0002-1282-5435)
- Κonstantinos Potaris (ORCID: https://orcid.org/0000-0001-6636-5078)
- Domenico Lo Tartaro (ORCID: https://orcid.org/0000-0001-7762-2535)
- Nikolaos Paschalidis (ORCID: https://orcid.org/0000-0001-6278-4144)
- Matthieu D. Lavigne (ORCID: https://orcid.org/0000-0003-1543-8745)
- Sofia Magkouta (ORCID: https://orcid.org/0000-0001-7143-3311)
- Maria Semitekolou (ORCID: https://orcid.org/0000-0002-0318-6774)
- Κonstantinos Samitas (ORCID: https://orcid.org/0000-0002-9921-9859)
- Aikaterini Tsitsopoulou
- Andrea Cossarizza (ORCID: https://orcid.org/0000-0002-5381-1558)
- Athina Varveri
- Dimitrios Mavroudis
- Alexandros Mavroudis
- Ioannis Kalomenidis
- Effrosyni Markaki
Institutions
- University of Modena and Reggio Emilia (IT)
- University of Crete (GR)
- Academy of Athens (GR)
Publication Details
- Journal
- iScience
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1016/j.isci.2025.112804
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Associazione Italiana per la Ricerca sul Cancro
- Hellenic Foundation for Research and Innovation
- European Regional Development Fund
- Competitiveness of Enterprises and Small and Medium-sized Enterprises