Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma

被引:0
作者
Sam, Ikuan [1 ,2 ]
Benhamouda, Nadine [1 ,2 ]
Biard, Lucie [3 ]
Da Meda, Laetitia [4 ]
Desseaux, Kristell [3 ]
Baroudjan, Barouyr [4 ]
Nakouri, Ines [4 ]
Renaud, Marion [4 ]
Sadoux, Aurelie [5 ]
Alkatrib, Marina [1 ]
Deleuze, Jean-Francois [6 ]
Battistella, Maxime [7 ]
Shen, Yimin [6 ]
Resche-Rigon, Matthieu [3 ]
Mourah, Samia [5 ,8 ]
Lebbe, Celeste [4 ]
Tartour, Eric [1 ,2 ]
机构
[1] Univ Paris Cite, INSERM, PARCC, Paris, France
[2] Hop Europeen Georges Pompidou HEGP, APHP, Hop Necker, Dept Immunol, Paris, France
[3] St Louis Hosp, APHP, Dept Biostat & Med Informat, ECSTRRA Team,INSERM,UMR 1153, Paris, France
[4] Univ Paris Cite, St Louis Hosp Paris, Canc Inst AP HP,INSERM U976, Nord Paris Cite,APHP Dermato Oncol, Paris, France
[5] Hop St Louis, Assistance Publ Hop Paris, Dept Pharmacol & Tumor Genom, Paris, France
[6] Ctr Etud Polymorphisme Humain CEPH Biobank, Fdn Jean Dausset CEPH, Paris, France
[7] Hop St Louis, Assistance Publ Hop Paris, Dept Pathol, Paris, France
[8] Univ Paris Cite, Team 1, Human Immunol Pathophysiol & Immunotherapy HIPI, INSERM UMR S 976, Paris, France
关键词
CD70-CD27; Interaction; Immunotherapy; Melanoma; Predictive Biomarker; Tumor Microenvironment; CTLA-4; BLOCKADE; PD-1; IMMUNOTHERAPY; BIOMARKERS; DISCOVERY; FRAMEWORK; SURVIVAL; PLACEBO; CANCER;
D O I
10.1038/s44321-025-00203-9
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:909 / 922
页数:14
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