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 language | English |
|---|---|
| Pages (from-to) | 114-121 |
| Number of pages | 8 |
| Journal | Cancer Treatment Reviews |
| Volume | 41 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 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
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 journal › Article
}
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 -