Plasma CD27, a Surrogate of the Intratumoral CD27-CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma

被引：22

作者：

Benhamouda, Nadine ^{[1
,2
]}

Sam, Ikuan ^{[1
]}

Epaillard, Nicolas ^{[1
]}

Gey, Alain ^{[1
,2
]}

Phan, Letuan ^{[3
]}

Pham, Hang Phuong ^{[4
]}

Gruel, Nadege ^{[5
,6
]}

Saldmann, Antonin ^{[1
,2
]}

Pineau, Josephine ^{[1
,2
]}

Hasan, Milena ^{[7
]}

Quiniou, Valentin ^{[4
]}

Nevoret, Camille ^{[8
,9
]}

Verkarre, Virginie ^{[10
]}

Libri, Valentina ^{[7
]}

Mella, Sebastien ^{[7
,11
]}

Granier, Clemence ^{[1
,2
]}

Broudin, Chloe ^{[10
]}

Ravel, Patrice ^{[12
]}

De Guillebon, Eleonore ^{[1
,13
]}

Mauge, Laetitia ^{[1
,14
]}

Helley, Dominique ^{[1
,14
]}

Jabla, Bernd ^{[7
,11
]}

Chaput, Nathalie ^{[15
]}

Albiges, Laurence ^{[16
]}

Katsahian, Sandrine ^{[8
,9
]}

Adam, Julien ^{[17
]}

Mejean, Arnaud ^{[18
]}

Adotevi, Olivier ^{[19
]}

Vano, Yann A. ^{[20
,21
]}

Oudard, Stephane ^{[1
,21
]}

Tartour, Eric ^{[1
,2
]}

机构：

[1] Univ Paris Cite, INSERM, PARCC, Paris, France

[2] Hop Europeen Georges Pompidou HEGP, AP HP, Dept Immunol, Paris, France

[3] Hop Europeen Georges Pompidou, ARTIC Assoc Rech Therapeut Innovantes Cancerol, Paris, France

[4] Parean Biotechnol, Depat Computat Biol, St Malo, France

[5] PSL Res Univ, Inst Curie Res Ctr, Childhood Tumors Lab, Equipe Labellisee Ligue Natl Canc Divers & Plast ,, Paris, France

[6] PSL Res Univ, Inst Curie Res Ctr, Dept Translat Res, Paris, France

[7] Inst Pasteur, Ctr Translat Sci, Cytometry & Biomarkers UTechS, Paris, France

[8] Univ Paris Cite, Ctr Rech Cordeliers, Epidemiol & Clin Res Unit, INSERM,UMRS 1138, Paris, France

[9] Ctr Invest Clin 1418, AP HP, HEGP, Paris, France

[10] Hop Europen Georges Pompidou, AP HP, Dept Pathol, 20 Rue Leblanc, F-75015 Paris, France

[11] CNRS USR, Inst Pasteur, Dept Computat Biol, Bioinformat & Biostat Hub, Paris, France

[12] Inst Rech Cancerol Montpellier, Bioinformat & Canc Syst Biol Team, IRCM INSERM U1194, Montpellier, France

[13] Inst Curie Hosp, Dept Med Oncol, Paris, France

[14] HEGP, Dept Hematol, Paris, France

[15] Univ Paris Saclay, Inst Gustave Roussy, Lab Immunomonitoring Oncol, Villejuif, France

[16] Univ Paris Saclay, Inst Gustave Roussy, Dept Med Oncol, Villejuif, France

[17] Univ Paris Saclay, Dept Biopathol, Gustave Roussy, Villejuif, France

[18] Hop Europeen Georges Pompidou, Dept Urol, Paris, France

[19] Univ Bourgogne Franche Comte, Univ Hosp Besancon, Dept Pneumol, INSERM EFS BFC,INSERM CIC1431, Besancon, France

[20] Sorbonne Univ, Univ Paris Cite, Ctr Rech Cordeliers, INSERM UMRS1138, Paris, France

[21] Hop Europeen Georges Pompidou, Dept Med Oncol, Paris, France

来源：

CLINICAL CANCER RESEARCH | 2022年 / 28卷 / 22期

关键词：

REDUCED CLINICAL BENEFIT; T-CELL; CD70; EXPRESSION; IMMUNE ESCAPE; SOLUBLE CD27; APOPTOSIS; COSTIMULATION; ACTIVATION; ANTIBODY; INFECTION;

D O I：

10.1158/1078-0432.CCR-22-0905

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear.Experimental Design: Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27 +/- T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then con-firmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immuno-therapy (35 for training cohort and 46 for validation cohort).Results: In the tumor microenvironment, CD27 +/- T cells inter-acted with CD70-expressing tumor cells. Compared with CD27- T cells, CD27 +/- T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27-CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti-programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy.Conclusions: In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expres-sion of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.

引用

页码：4983 / 4994

页数：12

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