Tumor Antigenicity and a Pre-Existing Adaptive Immune Response in Advanced BRAF Mutant Colorectal Cancers.

Autor: Bolzacchini E; Oncology Department, Sant'Anna Hospital, ASST-Lariana, 22100 Como, Italy.; 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., Libera L; 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., Church SE; NanoString Technologies Inc., Seattle, WA 98109, USA., Sahnane N; ASST Sette-Laghi, 21100 Varese, Italy., Bombelli R; 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., Digiacomo N; Oncologia Medica Humanitas Gavazzeni, 24125 Bergamo, Italy., Giordano M; Oncology Department, Sant'Anna Hospital, ASST-Lariana, 22100 Como, Italy., Petracco G; Pathology Department, Ospedale S. Anna, ASST Lariana, 22100 Como, Italy., Sessa F; 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.; ASST Sette-Laghi, 21100 Varese, Italy., Capella C; 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., Furlan D; 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.; ASST Sette-Laghi, 21100 Varese, Italy.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Aug 16; Vol. 14 (16). Date of Electronic Publication: 2022 Aug 16.
DOI: 10.3390/cancers14163951
Abstrakt: 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-naïve 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.
Databáze: MEDLINE
Externí odkaz: