Can we increase Immunogenicity in MSS Metastatic Colorectal Cancer (mCRC)? Guillem Argilés, MD Clinical Investigator Gastrointestinal Malignancies Program Early Drug Development Program Vall d’Hebron University Hospital Vall d'Hebron Institute of Oncology (VHIO)
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Can we increase Immunogenicity in MSS Metastatic ...•Understand the immune-biology of non-MSI colorectal cancer. •Review & discuss the results of the recently reported initiatives
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Can we increase Immunogenicity in MSS Metastatic Colorectal Cancer (mCRC)?
Guillem Argilés, MDClinical InvestigatorGastrointestinal Malignancies ProgramEarly Drug Development ProgramVall d’Hebron University HospitalVall d'Hebron Institute of Oncology (VHIO)
DISCLOSURE SLIDE:
- Personal financial interests, I received honoraria for advisory role,travel grants, research grants (past 5 years):
TGF-Beta activation inhibits anti-cellular immunity and causes unspecific inflammation:
Taurello Nat 2018 – Mariathasian Nat 2018
Bladder Cancer:
CRC:
Need for immune-biology biomarkers:
First generation immune-biomarkers Second generation immune-biomarkers:
Markers of hot tumors
MSI
Tumor mutation burden
PD-L1
Gene signatures
Multiplex IHC Cytof
Transcriptomic classification of mCRC
Guinney J, et al. Nat Med. 2015 - Becht E, et al. Clin Cancer Res. 2016
Disclaimer for CMS:
• CMS classifier was built to describe the different biologicalbackgrounds of colorectal cancer.
• The classification can not be used to take therapeutic decisions.
• For the purpose of this talk I am going to use CMS to depict thedifferent CRC populations at the molecular level and propose rational-based therapeutic approaches.
Transcriptomic classification of mCRC
Guinney J, et al. Nat Med. 2015 - Becht E, et al. Clin Cancer Res. 2016
• MSI• POLE mut.• BRCA mut.• BRCAness.• ARID 1
Therapeutic alternatives based on molecular background: