Expression pattern of immune checkpoint-associated molecules in radical nephrectomy specimens as a prognosticator in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.
To analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).



Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining.



Overall, 12 patients (19.3%) were revealed to be positive for PD-1-positive TILs, whereas positive expression of PD-L1 and PD-L2 were detected in 12 (19.3%) and 10 (16.1%) patients, respectively. Patients with positivePDL-L1 expression had significantly unfavorable progression-free survival (PFS) compared with those without positive PD-L1 expression, despite the remaining 2 molecules having no significant effect on PFS. Additionally, overall survival in patients positive for PD-1, PD-L1, or PD-L2 expression was significantly poorer than that in those without expression of each immune checkpoint-associated molecule. Multivariate analyses of several parameters identified the following independent prognosticators after the introduction of TKIs: PD-L1 expression status for PFS and lymph node metastasis, Memorial Sloan-Kettering Cancer Center classification and expression statuses of PD-1-positive TILs, and PD-L1 for overall survival.



Positive expression of immune checkpoint-associated molecules in tumor tissues could be useful prognosticators in patients with mRCC receiving TKIs as first-line systemic therapy.
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Takuto
T
Hara
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: hideakimiyake@hotmail.com.
Hideaki
H
Miyake
Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
Masato
M
Fujisawa
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D011505:Protein-Tyrosine Kinases
PD-1; PD-L1; PD-L2; Renal cell carcinoma; Tyrosine kinase inhibitor