title: [Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures].
abstract: The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance.
authors.affiliation: Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
authors.forename: I
authors.initials: I
authors.lastname: Peters
authors.affiliation: Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
authors.forename: H
authors.initials: H
authors.lastname: Tezval
authors.affiliation: Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
authors.forename: M W
authors.initials: MW
authors.lastname: Kramer
authors.affiliation: Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
authors.forename: M
authors.initials: M
authors.lastname: Wolters
authors.affiliation: Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover.
authors.forename: V
authors.initials: V
authors.lastname: Grünwald
authors.affiliation: Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
authors.forename: M A
authors.initials: MA
authors.lastname: Kuczyk
authors.affiliation: Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover.
authors.forename: J
authors.initials: J
authors.lastname: Serth
mesh_terms: D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D030541:Databases, Genetic; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009392:Nephrectomy; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013223:Statistics as Topic; D015996:Survival Rate
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger