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

93 Citations (Scopus)

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

Fingerprint

Renal Cell Carcinoma
Neoplasms
Therapeutics
Lymphocytes
T-Lymphocytes
Immune Evasion
Angiogenesis Inhibitors
Allergy and Immunology
Immune System
Immunity
Down-Regulation
Cell Proliferation
Ligands
Antibodies
Growth

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., ... 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

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

In: Cancer Treatment Reviews, Vol. 41, No. 2, 01.02.2015, p. 114-121.

Research output: Contribution to journalArticle

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, vol. 41, no. 2, pp. 114-121. https://doi.org/10.1016/j.ctrv.2014.12.013
Massari F, Santoni M, Ciccarese C, Santini D, Alfieri S, Martignoni G et al. PD-1 blockade therapy in renal cell carcinoma: Current studies and future promises. Cancer Treatment Reviews. 2015 Feb 1;41(2):114-121. https://doi.org/10.1016/j.ctrv.2014.12.013
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. / PD-1 blockade therapy in renal cell carcinoma : Current studies and future promises. In: Cancer Treatment Reviews. 2015 ; Vol. 41, No. 2. pp. 114-121.
@article{1470307d56f145ae93821bb12eca6f6a,
title = "PD-1 blockade therapy in renal cell carcinoma: Current studies and future promises",
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.",
keywords = "Immunotherapy, PD-1, PDL-1, Renal cell carcinoma",
author = "F. Massari and M. Santoni and C. Ciccarese and D. Santini and S. Alfieri and G. Martignoni and M. Brunelli and F. Piva and R. Berardi and R. Montironi and C. Porta and S. Cascinu and G. Tortora",
year = "2015",
month = "2",
day = "1",
doi = "10.1016/j.ctrv.2014.12.013",
language = "English",
volume = "41",
pages = "114--121",
journal = "Cancer Treatment Reviews",
issn = "0305-7372",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - PD-1 blockade therapy in renal cell carcinoma

T2 - Current studies and future promises

AU - Massari, F.

AU - Santoni, M.

AU - Ciccarese, C.

AU - Santini, D.

AU - Alfieri, S.

AU - Martignoni, G.

AU - Brunelli, M.

AU - Piva, F.

AU - Berardi, R.

AU - Montironi, R.

AU - Porta, C.

AU - Cascinu, S.

AU - Tortora, G.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Immunotherapy

KW - PD-1

KW - PDL-1

KW - Renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=84921779027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921779027&partnerID=8YFLogxK

U2 - 10.1016/j.ctrv.2014.12.013

DO - 10.1016/j.ctrv.2014.12.013

M3 - Article

C2 - 25586601

AN - SCOPUS:84921779027

VL - 41

SP - 114

EP - 121

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

SN - 0305-7372

IS - 2

ER -