Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma
Abstract Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of...
| Published in: | EMBO Molecular Medicine |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2025-03-01
|
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s44321-025-00203-9 |
| _version_ | 1849629648314433536 |
|---|---|
| author | Ikuan Sam Nadine Benhamouda Lucie Biard Laetitia Da Meda Kristell Desseaux Barouyr Baroudjan Ines Nakouri Marion Renaud Aurélie Sadoux Marina Alkatrib Jean-François Deleuze Maxime Battistella Yimin Shen Matthieu Resche-Rigon Samia Mourah Celeste Lebbe Eric Tartour |
| author_facet | Ikuan Sam Nadine Benhamouda Lucie Biard Laetitia Da Meda Kristell Desseaux Barouyr Baroudjan Ines Nakouri Marion Renaud Aurélie Sadoux Marina Alkatrib Jean-François Deleuze Maxime Battistella Yimin Shen Matthieu Resche-Rigon Samia Mourah Celeste Lebbe Eric Tartour |
| author_sort | Ikuan Sam |
| collection | DOAJ |
| container_title | EMBO Molecular Medicine |
| description | Abstract Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of CD70-CD27 and dysfunctional T cells in the tumor microenvironment of renal cell carcinoma. In this study, we first characterized the intratumoral expression of CD70 and CD27 in melanoma tumors and their interaction in vivo. We then reported a significant association between baseline sCD27 and anti-PD-1 resistance as assessed by progression-free survival, overall survival, or 12-month complete response in two prospective cohorts of melanoma patients. Multivariate analysis confirmed that sCD27 was independently associated with clinical outcomes. Notably, sCD27 did not predict clinical response to combination therapy in either cohort. This differential predictive value of sCD27 for the two therapeutic options was later confirmed by propensity score analysis. Our results suggest that high plasma sCD27 levels predict poorer efficacy of anti-PD1 monotherapy in metastatic melanoma, justifying therapeutic escalation with a combination of anti-PD1 and anti-CTLA-4. |
| format | Article |
| id | doaj-art-1eba24e46f9f4dd789a43a181bb2fdff |
| institution | Directory of Open Access Journals |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| spelling | doaj-art-1eba24e46f9f4dd789a43a181bb2fdff2025-08-20T02:25:16ZengSpringer NatureEMBO Molecular Medicine1757-46842025-03-0117590992210.1038/s44321-025-00203-9Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanomaIkuan Sam0Nadine Benhamouda1Lucie Biard2Laetitia Da Meda3Kristell Desseaux4Barouyr Baroudjan5Ines Nakouri6Marion Renaud7Aurélie Sadoux8Marina Alkatrib9Jean-François Deleuze10Maxime Battistella11Yimin Shen12Matthieu Resche-Rigon13Samia Mourah14Celeste Lebbe15Eric Tartour16Universite Paris Cite, INSERM, PARCCUniversite Paris Cite, INSERM, PARCCAPHP, Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, Paris, INSERM, UMR-1153, ECSTRRA TeamUniversite Paris Cité, APHP Dermato-Oncology, Cancer Institute AP-HP, Nord Paris Cité, INSERM U976, Saint Louis Hospital ParisAPHP, Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, Paris, INSERM, UMR-1153, ECSTRRA TeamUniversite Paris Cité, APHP Dermato-Oncology, Cancer Institute AP-HP, Nord Paris Cité, INSERM U976, Saint Louis Hospital ParisUniversite Paris Cité, APHP Dermato-Oncology, Cancer Institute AP-HP, Nord Paris Cité, INSERM U976, Saint Louis Hospital ParisUniversite Paris Cité, APHP Dermato-Oncology, Cancer Institute AP-HP, Nord Paris Cité, INSERM U976, Saint Louis Hospital ParisDepartment of Pharmacology and Tumor Genomics, Hôpital Saint Louis, Assistance Publique-Hôpitaux de ParisUniversite Paris Cite, INSERM, PARCCFondation Jean Dausset-CEPH (Centre d’Etude du Polymorphisme Humain), CEPH-BiobankDepartment of Pathology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de ParisFondation Jean Dausset-CEPH (Centre d’Etude du Polymorphisme Humain), CEPH-BiobankAPHP, Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, Paris, INSERM, UMR-1153, ECSTRRA TeamDepartment of Pharmacology and Tumor Genomics, Hôpital Saint Louis, Assistance Publique-Hôpitaux de ParisUniversite Paris Cité, APHP Dermato-Oncology, Cancer Institute AP-HP, Nord Paris Cité, INSERM U976, Saint Louis Hospital ParisUniversite Paris Cite, INSERM, PARCCAbstract Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of CD70-CD27 and dysfunctional T cells in the tumor microenvironment of renal cell carcinoma. In this study, we first characterized the intratumoral expression of CD70 and CD27 in melanoma tumors and their interaction in vivo. We then reported a significant association between baseline sCD27 and anti-PD-1 resistance as assessed by progression-free survival, overall survival, or 12-month complete response in two prospective cohorts of melanoma patients. Multivariate analysis confirmed that sCD27 was independently associated with clinical outcomes. Notably, sCD27 did not predict clinical response to combination therapy in either cohort. This differential predictive value of sCD27 for the two therapeutic options was later confirmed by propensity score analysis. Our results suggest that high plasma sCD27 levels predict poorer efficacy of anti-PD1 monotherapy in metastatic melanoma, justifying therapeutic escalation with a combination of anti-PD1 and anti-CTLA-4.https://doi.org/10.1038/s44321-025-00203-9CD70-CD27 InteractionImmunotherapyMelanomaPredictive BiomarkerTumor Microenvironment |
| spellingShingle | Ikuan Sam Nadine Benhamouda Lucie Biard Laetitia Da Meda Kristell Desseaux Barouyr Baroudjan Ines Nakouri Marion Renaud Aurélie Sadoux Marina Alkatrib Jean-François Deleuze Maxime Battistella Yimin Shen Matthieu Resche-Rigon Samia Mourah Celeste Lebbe Eric Tartour Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma CD70-CD27 Interaction Immunotherapy Melanoma Predictive Biomarker Tumor Microenvironment |
| title | Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma |
| title_full | Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma |
| title_fullStr | Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma |
| title_full_unstemmed | Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma |
| title_short | Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma |
| title_sort | soluble cd27 differentially predicts resistance to anti pd1 alone but not with anti ctla 4 in melanoma |
| topic | CD70-CD27 Interaction Immunotherapy Melanoma Predictive Biomarker Tumor Microenvironment |
| url | https://doi.org/10.1038/s44321-025-00203-9 |
| work_keys_str_mv | AT ikuansam solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT nadinebenhamouda solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT luciebiard solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT laetitiadameda solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT kristelldesseaux solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT barouyrbaroudjan solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT inesnakouri solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT marionrenaud solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT aureliesadoux solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT marinaalkatrib solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT jeanfrancoisdeleuze solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT maximebattistella solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT yiminshen solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT matthieurescherigon solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT samiamourah solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT celestelebbe solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma AT erictartour solublecd27differentiallypredictsresistancetoantipd1alonebutnotwithantictla4inmelanoma |