Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer: possible implications for immunotherapy

Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer : possible implications for immunotherapy

Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC.Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients.Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts.Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.

Gylling, Björn,1978-Umeå universitet,Patologi(Swepub:umu)bjgy0001 (författare)
Li, XingruUmeå universitet,Patologi(Swepub:umu)xili0010 (författare)
Stenberg, Åsa,1973-Umeå universitet,Patologi(Swepub:umu)asastg00 (författare)
Löfgren Burström, AnnaUmeå universitet,Patologi(Swepub:umu)anlo0002 (författare)
Zingmark, Carl,1975-Umeå universitet,Patologi(Swepub:umu)cazi0001 (författare)
van Guelpen, BethanyUmeå universitet,Institutionen för strålningsvetenskaper,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)(Swepub:umu)beyvan99 (författare)
Ljuslinder, Ingrid,1968-Umeå universitet,Institutionen för strålningsvetenskaper(Swepub:umu)inlj0001 (författare)
Ling, AgnesUmeå universitet,Patologi(Swepub:umu)agslig01 (författare)
Palmqvist, RichardUmeå universitet,Patologi(Swepub:umu)ripa0001 (författare)
Umeå universitetPatologi (creator_code:org_t)

Av författaren/redakt...: Edin, Sofia; Gylling, Björn, ...; Li, Xingru; Stenberg, Åsa, 1 ...; Löfgren Burström ...; Zingmark, Carl, ...; visa fler...; van Guelpen, Bet ...; Ljuslinder, Ingr ...; Ling, Agnes; Palmqvist, Richa ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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