Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma
Purpose Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.Experimental design In this translational study, cl...
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010421.full |
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| author | Teresa Troiani Fabiana Napolitano Luigi Formisano Roberto Bianco Daniela Russo Daniela Esposito Giuseppe Ercolano Angela Ianaro Alberto Servetto Daniela Claudia Maresca Marcella Scala Annarita Amato Stefania Belli Claudia Maria Ascione Angela Vallefuoco Giovanna Attanasio Fabio Somma Silvia Varricchio Massimo Mascolo Claudia Costa Alessia Villani Massimiliano Scalvenzi Gianfranco Orlandino |
| author_facet | Teresa Troiani Fabiana Napolitano Luigi Formisano Roberto Bianco Daniela Russo Daniela Esposito Giuseppe Ercolano Angela Ianaro Alberto Servetto Daniela Claudia Maresca Marcella Scala Annarita Amato Stefania Belli Claudia Maria Ascione Angela Vallefuoco Giovanna Attanasio Fabio Somma Silvia Varricchio Massimo Mascolo Claudia Costa Alessia Villani Massimiliano Scalvenzi Gianfranco Orlandino |
| author_sort | Teresa Troiani |
| collection | DOAJ |
| description | Purpose Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.Experimental design In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.Results First, we investigated the baseline characteristics of the immune landscape of cSCC biopsies. Gene Set Enrichment Analysis showed upregulation of interleukin (IL)2/STAT5 pathways and downregulation of Interferon signatures in non-responder patients compared with responders. Next, we studied the early changes induced by cemiplimab in tissue biopsies. Notably, after only three weeks, cemiplimab treatment induced an increase in B cells and CD8+ T cells in responders, whereas their abundance decreased in non-responder patients. Moreover, analyzing differentially expressed genes modulated early during treatment, compared with baseline biopsies, we found that IL1β and IL8 exhibited early downregulation in responder patients’ tumor specimens. We assessed whether changes in the local tumor microenvironment were mirrored in peripheral blood. Similar to tissue findings, no changes were observed in the whole T regulatory (Treg) population, although PD1+ Tregs, which were downregulated in responder patients (vs T0), showed a rebound enrichment in non-responders after three cycles of cemiplimab. Finally, IL8 mirrored the tissue results, unlike IL1β, with early (T1) and then sustained (T3) downregulation of its levels in responder patients, while increased in non-responders.Conclusions Taken together, these findings shed light on the significance of early transcriptomic and immune cell modulation in predicting responses to cemiplimab therapy. Additionally, our data suggest that IL8 levels in peripheral blood offer promising avenues for personalized treatment selection and response assessment in patients with cSCC receiving cemiplimab, while PD1+Tregs can be followed longitudinally to monitor response to therapy. |
| format | Article |
| id | doaj-art-d8ff3c0658eb4915b326e1166d2bff05 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d8ff3c0658eb4915b326e1166d2bff052025-01-27T08:15:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010421Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinomaTeresa Troiani0Fabiana Napolitano1Luigi Formisano2Roberto Bianco3Daniela Russo4Daniela Esposito5Giuseppe Ercolano6Angela Ianaro7Alberto Servetto8Daniela Claudia Maresca9Marcella Scala10Annarita Amato11Stefania Belli12Claudia Maria Ascione13Angela Vallefuoco14Giovanna Attanasio15Fabio Somma16Silvia Varricchio17Massimo Mascolo18Claudia Costa19Alessia Villani20Massimiliano Scalvenzi21Gianfranco Orlandino22Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyPathology Unit, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyClinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyPathology Unit, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, ItalyPathology Unit, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, ItalySection of Dermatology, Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalySection of Dermatology, Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalySection of Dermatology, Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Plastic and Reconstructive Surgery, University of Naples Federico II, Naples, ItalyPurpose Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.Experimental design In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.Results First, we investigated the baseline characteristics of the immune landscape of cSCC biopsies. Gene Set Enrichment Analysis showed upregulation of interleukin (IL)2/STAT5 pathways and downregulation of Interferon signatures in non-responder patients compared with responders. Next, we studied the early changes induced by cemiplimab in tissue biopsies. Notably, after only three weeks, cemiplimab treatment induced an increase in B cells and CD8+ T cells in responders, whereas their abundance decreased in non-responder patients. Moreover, analyzing differentially expressed genes modulated early during treatment, compared with baseline biopsies, we found that IL1β and IL8 exhibited early downregulation in responder patients’ tumor specimens. We assessed whether changes in the local tumor microenvironment were mirrored in peripheral blood. Similar to tissue findings, no changes were observed in the whole T regulatory (Treg) population, although PD1+ Tregs, which were downregulated in responder patients (vs T0), showed a rebound enrichment in non-responders after three cycles of cemiplimab. Finally, IL8 mirrored the tissue results, unlike IL1β, with early (T1) and then sustained (T3) downregulation of its levels in responder patients, while increased in non-responders.Conclusions Taken together, these findings shed light on the significance of early transcriptomic and immune cell modulation in predicting responses to cemiplimab therapy. Additionally, our data suggest that IL8 levels in peripheral blood offer promising avenues for personalized treatment selection and response assessment in patients with cSCC receiving cemiplimab, while PD1+Tregs can be followed longitudinally to monitor response to therapy.https://jitc.bmj.com/content/13/1/e010421.full |
| spellingShingle | Teresa Troiani Fabiana Napolitano Luigi Formisano Roberto Bianco Daniela Russo Daniela Esposito Giuseppe Ercolano Angela Ianaro Alberto Servetto Daniela Claudia Maresca Marcella Scala Annarita Amato Stefania Belli Claudia Maria Ascione Angela Vallefuoco Giovanna Attanasio Fabio Somma Silvia Varricchio Massimo Mascolo Claudia Costa Alessia Villani Massimiliano Scalvenzi Gianfranco Orlandino Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma Journal for ImmunoTherapy of Cancer |
| title | Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma |
| title_full | Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma |
| title_fullStr | Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma |
| title_full_unstemmed | Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma |
| title_short | Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma |
| title_sort | early assessment of il8 and pd1 treg predicts response and guides treatment monitoring in cemiplimab treated cutaneous squamous cell carcinoma |
| url | https://jitc.bmj.com/content/13/1/e010421.full |
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