Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients.
The role of Cytomegalovirus (CMV) in carcinogenesis is controversial. We studied whether CMV may contribute to cancer occurrence in renal transplant recipients. We studied a prospective cohort of 455 consecutive patients who received a kidney transplant between January 1995 and December 2006. All cancers and types of cancers were assessed. Lymphocyte phenotype and cytokines production were analysed according to CMV status in a subset population of this cohort. Mean follow-up was 84 ± 29 months. One hundred and nineteen cancers (26.2%) occurred during the study follow-up. There was a higher cumulated incidence of cancers in CMV-exposed patients (30.4% vs. 20%; P=0.018). Mean time to cancer occurrence was shorter in CMV-exposed patients than in CMV-naïve patients (4.7 ± 2.6 vs. 6.7 ± 2.8; P = 0.001). Cox regression analysis revealed that both pretransplant CMV exposure (HR, 1.83; 95% CI, 1.17-2.88; P = 0.009) and post-transplant CMV replication (HR, 2.17; 95% CI, 1.02-4.59; P = 0.044) were risk factors for cancer. Among CD8+ T cells, exhausted T cells assessed as CD57+CD28- were expanded in CMV-exposed patients (26 ± 20 vs. 9 ± 8%; P < 0.0001), whereas CD8+CD57+IL2- cells were more frequent in CMV-exposed patients. Our results highly suggest that CMV increases the risk of cancer after transplantation.
INSERM, UMR645, Besançon, France. ccourivaud@chu-besancon.fr
Cécile
C
Courivaud
Jamal
J
Bamoulid
Béatrice
B
Gaugler
Caroline
C
Roubiou
Charlène
C
Arregui
Jean-Marc
JM
Chalopin
Christophe
C
Borg
Pierre
P
Tiberghien
Marie-Christine
MC
Woronoff-Lemsi
Philippe
P
Saas
Didier
D
Ducloux
D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000096:biosynthesis; D018959:CD57 Antigens / Q000096:biosynthesis; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007107:Immune System; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000276:immunology* / Q000821:virology; D010641:Phenotype; D011446:Prospective Studies; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000150:complications / Q000628:therapy* / Q000821:virology; D012306:Risk; D016896:Treatment Outcome
D018106:CD28 Antigens; D018959:CD57 Antigens