PMID- 33435262
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231110
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 2
DP  - 2021 Jan 10
TI  - Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune 
      Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma 
      (mccRCC).
LID - 10.3390/cancers13020231 [doi]
LID - 231
AB  - Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy 
      with an increasing incidence in developed countries. Despite a greater 
      understanding of the cancer biology, which has led to an increase of therapeutic 
      options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor 
      prognosis with a median five-years survival rate lower than 10%. The standard of 
      care for mccRCC has changed dramatically over the past decades with the emergence 
      of new treatments: anti-VEGFR tyrosine kinase inhibitors, mTOR Inhibitors and 
      immune checkpoint inhibitors (ICI) such as anti-Programmed cell-Death 1 (PD-1) 
      and anti-anti-Programmed Death Ligand-1 (PD-L1) used as monotherapy or as a 
      combination with anti CTLA-4 or anti angiogenic therapies. In the face of these 
      rising therapeutic options, the question of the therapeutic sequences is crucial. 
      Predictive biomarkers are urgently required to provide a personalized treatment 
      for each patient. Disappointingly, the usual ICI biomarkers, PD-L1 expression and 
      Tumor Mutational Burden, approved in melanoma or non-small cell lung cancer 
      (NSCLC) have failed to distinguish good and poor mccRCC responders to ICI. The 
      tumor microenvironment is known to be involved in ICI response. Innovative 
      technologies can be used to explore the immune contexture of tumors and to find 
      predictive and prognostic biomarkers. Recent comprehensive molecular 
      characterization of RCC has led to the development of robust genomic signatures, 
      which could be used as predictive biomarkers. This review will provide an 
      overview of the components of the RCC tumor microenvironment and discuss their 
      role in disease progression and resistance to ICI. We will then highlight the 
      current and future ICI predictive biomarkers assessed in mccRCC with a major 
      focus on immunohistochemistry markers and genomic signatures.
FAU - Simonaggio, Audrey
AU  - Simonaggio A
AD  - Medical Oncology, Hopital Europeen Georges Pompidou, APHP Centre-Universite de 
      Paris, 75015 Paris, France.
FAU - Epaillard, Nicolas
AU  - Epaillard N
AUID- ORCID: 0000-0001-7543-491X
AD  - Medical Oncology, Hopital Europeen Georges Pompidou, APHP Centre-Universite de 
      Paris, 75015 Paris, France.
FAU - Pobel, Cedric
AU  - Pobel C
AD  - Medical Oncology, Hopital Europeen Georges Pompidou, APHP Centre-Universite de 
      Paris, 75015 Paris, France.
FAU - Moreira, Marco
AU  - Moreira M
AUID- ORCID: 0000-0002-9933-7767
AD  - INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team "Cancer, Immune 
      Control and Escape", University Paris Descartes Paris 5, Sorbonne Paris Cite, 
      F-75006 Paris, France.
FAU - Oudard, Stephane
AU  - Oudard S
AD  - Medical Oncology, Hopital Europeen Georges Pompidou, APHP Centre-Universite de 
      Paris, 75015 Paris, France.
AD  - INSERM UMR-S1147, Universite de Paris, Sorbonne Universite, 75006 Paris, France.
FAU - Vano, Yann-Alexandre
AU  - Vano YA
AD  - Medical Oncology, Hopital Europeen Georges Pompidou, APHP Centre-Universite de 
      Paris, 75015 Paris, France.
AD  - INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team "Cancer, Immune 
      Control and Escape", University Paris Descartes Paris 5, Sorbonne Paris Cite, 
      F-75006 Paris, France.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210110
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7827724
OTO - NOTNLM
OT  - biomarker
OT  - clear cell renal cell carcinoma
OT  - genomic signature
OT  - immune checkpoint inhibitors
OT  - transcriptomic analysis
COIS- Yann-Alexandre Vano and Stephane Oudard: consulting fees from BMS, MSD, Pfizer, 
      Novartis, Ipsen, Roche, Astellas, Sanofi and Janssen. No potential conflicts of 
      interest were disclosed by the other authors.
EDAT- 2021/01/14 06:00
MHDA- 2021/01/14 06:01
PMCR- 2021/01/10
CRDT- 2021/01/13 01:01
PHST- 2020/11/07 00:00 [received]
PHST- 2020/12/18 00:00 [revised]
PHST- 2020/12/29 00:00 [accepted]
PHST- 2021/01/13 01:01 [entrez]
PHST- 2021/01/14 06:00 [pubmed]
PHST- 2021/01/14 06:01 [medline]
PHST- 2021/01/10 00:00 [pmc-release]
AID - cancers13020231 [pii]
AID - cancers-13-00231 [pii]
AID - 10.3390/cancers13020231 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Jan 10;13(2):231. doi: 10.3390/cancers13020231.