PD-1 blockade therapy in renal cell carcinoma: Current studies and future promises

F. Massari, M. Santoni, C. Ciccarese, D. Santini, S. Alfieri, G. Martignoni, M. Brunelli, F. Piva, R. Berardi, R. Montironi, C. Porta, S. Cascinu, G. Tortora

Research output: Contribution to journalArticle

Abstract

RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC.In this review we discuss the role of PD-1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies and promising therapeutic perspectives to target the PD-1 pathway.

Original languageEnglish
Pages (from-to)114-121
Number of pages8
JournalCancer Treatment Reviews
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

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Keywords

  • Immunotherapy
  • PD-1
  • PDL-1
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Massari, F., Santoni, M., Ciccarese, C., Santini, D., Alfieri, S., Martignoni, G., Brunelli, M., Piva, F., Berardi, R., Montironi, R., Porta, C., Cascinu, S., & Tortora, G. (2015). PD-1 blockade therapy in renal cell carcinoma: Current studies and future promises. Cancer Treatment Reviews, 41(2), 114-121. https://doi.org/10.1016/j.ctrv.2014.12.013