Multimarker assessment of B cell and plasma cell subsets and their prognostic role in the colorectal cancer microenvironment
Sirkiä, Onni; Karjalainen, Henna; Elomaa, Hanna; Väyrynen, Sara A; Tuomisto, Anne; Sirniö, Päivi; Äijälä, Ville K; Tapiainen, Vilja V; Kastinen, Meeri; Wirta, Erkki-Ville; Helminen, Olli; Meriläinen, Sanna; Rintala, Jukka; Saarnio, Juha; Rautio, Tero; Seppälä, Toni T; Mäkinen, Markus J; Mecklin, Jukka-Pekka; Böhm, Jan; Ahtiainen, Maarit; Väyrynen, Juha P (2025-05-07)
Association for Cancer Research
07.05.2025
Onni Sirkiä, Henna Karjalainen, Hanna Elomaa, Sara A. Väyrynen, Anne Tuomisto, Päivi Sirniö, Ville K. Äijälä, Vilja V. Tapiainen, Meeri Kastinen, Erkki-Ville Wirta, Olli Helminen, Sanna Meriläinen, Jukka Rintala, Juha Saarnio, Tero Rautio, Toni T. Seppälä, Markus J. Mäkinen, Jukka-Pekka Mecklin, Jan Böhm, Maarit Ahtiainen, Juha P. Väyrynen; Multimarker Assessment of B-Cell and Plasma Cell Subsets and Their Prognostic Role in the Colorectal Cancer Microenvironment. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-4083
https://creativecommons.org/licenses/by/4.0/
© 2025 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
https://creativecommons.org/licenses/by/4.0/
© 2025 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202505083154
https://urn.fi/URN:NBN:fi:oulu-202505083154
Tiivistelmä
Abstract
Purpose:
Although the association between cytotoxic T lymphocytes and favorable prognosis in colorectal cancer is well established, the prognostic significance of B lymphocytes remains more ambiguous. This study aimed to assess the characteristics and significance of various B-cell and plasma cell subsets in colorectal tumors.
Experimental Design:
We designed a seven-plex IHC assay, combined with machine learning–based image analysis, to identify various B-cell and plasma cell populations and applied it to study a cohort of 912 colorectal tumors. We assessed the prognostic significance of B-cell and plasma cell densities using Kaplan–Meier estimators and Cox regression models. Additionally, we designed a more clinically applicable three-plex assay, which we used to study B-cell and plasma cell densities in a separate validation cohort of 737 patients.
Results:
High plasma cell density in the center of the tumor was associated with longer cancer-specific survival independent of disease stage, mismatch repair status, T-cell densities, and other covariates. In the study cohort, the multivariable HR for high (vs. low) plasma cell density was 0.48 (95% confidence interval, 0.32–0.72; Ptrend = 0.0005), whereas the corresponding HR in the validation cohort was 0.37 (95% confidence interval, 0.21–0.65; Ptrend = 0.0003). Of the specific subsets, IgG1–IgG2– plasma cells showed the strongest association with improved survival. High B-cell densities were not independently associated with a better prognosis.
Conclusions:
Plasma cell densities in the center of the tumor represent a relevant tumor-immune biomarker in colorectal cancer, complementing T-cell density measurements.
Purpose:
Although the association between cytotoxic T lymphocytes and favorable prognosis in colorectal cancer is well established, the prognostic significance of B lymphocytes remains more ambiguous. This study aimed to assess the characteristics and significance of various B-cell and plasma cell subsets in colorectal tumors.
Experimental Design:
We designed a seven-plex IHC assay, combined with machine learning–based image analysis, to identify various B-cell and plasma cell populations and applied it to study a cohort of 912 colorectal tumors. We assessed the prognostic significance of B-cell and plasma cell densities using Kaplan–Meier estimators and Cox regression models. Additionally, we designed a more clinically applicable three-plex assay, which we used to study B-cell and plasma cell densities in a separate validation cohort of 737 patients.
Results:
High plasma cell density in the center of the tumor was associated with longer cancer-specific survival independent of disease stage, mismatch repair status, T-cell densities, and other covariates. In the study cohort, the multivariable HR for high (vs. low) plasma cell density was 0.48 (95% confidence interval, 0.32–0.72; Ptrend = 0.0005), whereas the corresponding HR in the validation cohort was 0.37 (95% confidence interval, 0.21–0.65; Ptrend = 0.0003). Of the specific subsets, IgG1–IgG2– plasma cells showed the strongest association with improved survival. High B-cell densities were not independently associated with a better prognosis.
Conclusions:
Plasma cell densities in the center of the tumor represent a relevant tumor-immune biomarker in colorectal cancer, complementing T-cell density measurements.
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