PMID- 36010943
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 16
DP  - 2022 Aug 16
TI  - Tumor Antigenicity and a Pre-Existing Adaptive Immune Response in Advanced BRAF 
      Mutant Colorectal Cancers.
LID - 10.3390/cancers14163951 [doi]
LID - 3951
AB  - The main hypothesis of this study is that gene expression profiles (GEPs) 
      integrating both tumor antigenicity and a pre-existing adaptive immune response 
      can be used to generate distinct immune-related signatures of BRAF mutant 
      colorectal cancers (BRAF-CRCs) to identify actionable biomarkers predicting 
      response to immunotherapy. GEPs of 89 immunotherapy-naive BRAF-CRCs were 
      generated using the Pan-Cancer IO 360 gene expression panel and the NanoString 
      nCounter platform and were correlated with microsatellite instability (MSI) 
      status and with CD8+ tumor-infiltrating lymphocyte (TIL) content. Hot/inflamed 
      profiles were found in 52% of all cases, and high scores of Tumor Inflammation 
      Signature were observed in 42% of the metastatic BRAF-CRCs. A subset of MSI 
      tumors showed a cold profile. Antigen Processing Machinery (APM) signature was 
      not differentially expressed in MSI tumors compared with MSS cases. By contrast, 
      the APM signature was significantly upregulated in CD8+ BRAF-CRCs versus CD8- 
      tumors. Our study demonstrates that a significant fraction of BRAF-CRCs may be a 
      candidate for immunotherapy and that the simultaneous analysis of MSI status and 
      CD8+ TIL content increases accuracy in identifying patients who can potentially 
      benefit from immune checkpoint inhibitors. GEPs may be very useful in expanding 
      the spectrum of patients with BRAF-CRCs who can benefit from immune checkpoint 
      blockade.
FAU - Bolzacchini, Elena
AU  - Bolzacchini E
AD  - Oncology Department, Sant'Anna Hospital, ASST-Lariana, 22100 Como, Italy.
AD  - Unit of Pathology, Department of Medicine and Surgery and Research Center for the 
      Study of Hereditary and Familial Tumors, University of Insubria, 21100 Varese, 
      Italy.
FAU - Libera, Laura
AU  - Libera L
AUID- ORCID: 0000-0003-2130-6669
AD  - Unit of Pathology, Department of Medicine and Surgery and Research Center for the 
      Study of Hereditary and Familial Tumors, University of Insubria, 21100 Varese, 
      Italy.
FAU - Church, Sarah E
AU  - Church SE
AD  - NanoString Technologies Inc., Seattle, WA 98109, USA.
FAU - Sahnane, Nora
AU  - Sahnane N
AD  - ASST Sette-Laghi, 21100 Varese, Italy.
FAU - Bombelli, Raffaella
AU  - Bombelli R
AD  - Unit of Pathology, Department of Medicine and Surgery and Research Center for the 
      Study of Hereditary and Familial Tumors, University of Insubria, 21100 Varese, 
      Italy.
FAU - Digiacomo, Nunzio
AU  - Digiacomo N
AD  - Oncologia Medica Humanitas Gavazzeni, 24125 Bergamo, Italy.
FAU - Giordano, Monica
AU  - Giordano M
AD  - Oncology Department, Sant'Anna Hospital, ASST-Lariana, 22100 Como, Italy.
FAU - Petracco, Guido
AU  - Petracco G
AD  - Pathology Department, Ospedale S. Anna, ASST Lariana, 22100 Como, Italy.
FAU - Sessa, Fausto
AU  - Sessa F
AD  - Unit of Pathology, Department of Medicine and Surgery and Research Center for the 
      Study of Hereditary and Familial Tumors, University of Insubria, 21100 Varese, 
      Italy.
AD  - ASST Sette-Laghi, 21100 Varese, Italy.
FAU - Capella, Carlo
AU  - Capella C
AD  - Unit of Pathology, Department of Medicine and Surgery and Research Center for the 
      Study of Hereditary and Familial Tumors, University of Insubria, 21100 Varese, 
      Italy.
FAU - Furlan, Daniela
AU  - Furlan D
AUID- ORCID: 0000-0002-5958-5379
AD  - Unit of Pathology, Department of Medicine and Surgery and Research Center for the 
      Study of Hereditary and Familial Tumors, University of Insubria, 21100 Varese, 
      Italy.
AD  - ASST Sette-Laghi, 21100 Varese, Italy.
LA  - eng
PT  - Journal Article
DEP - 20220816
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9405961
OTO - NOTNLM
OT  - BRAF mutation
OT  - CD8+
OT  - MHC Class I antigen
OT  - MSI
OT  - NanoString
OT  - PanCancer IO 360
OT  - colorectal cancer
OT  - immune checkpoint inhibitors
COIS- S.E.C. is an employee of NanoString Technologies Inc. (Seattle, WA, USA). The 
      remaining authors declare no conflict of interest.
EDAT- 2022/08/27 06:00
MHDA- 2022/08/27 06:01
PMCR- 2022/08/16
CRDT- 2022/08/26 01:14
PHST- 2022/07/19 00:00 [received]
PHST- 2022/08/09 00:00 [revised]
PHST- 2022/08/15 00:00 [accepted]
PHST- 2022/08/26 01:14 [entrez]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/08/27 06:01 [medline]
PHST- 2022/08/16 00:00 [pmc-release]
AID - cancers14163951 [pii]
AID - cancers-14-03951 [pii]
AID - 10.3390/cancers14163951 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Aug 16;14(16):3951. doi: 10.3390/cancers14163951.