biostudies-literatureAkimoto NMassachusetts General HospitalAmerican Cancer SocietyMitsukoshi Health and Welfare FoundationAmerican Society of Clinical OncologyNCI NIH HHSUehara Memorial FoundationNational Institutes of HealthHuazhong University of Science and TechnologyAmerican Association for Cancer ResearchJapan Society for the Promotion of Science840198https://www.ebi.ac.uk/biostudies/studies/S-EPMC8980356biostudies-literatureUnknown13<h4>Background</h4>The relationships between tumor stromal features (such as desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles) and immune cells in the colorectal carcinoma microenvironment have not yet been fully characterized.<h4>Methods</h4>In 908 tumors with available tissue among 4,465 incident colorectal adenocarcinoma cases in two prospective cohort studies, we examined desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles. We conducted multiplex immunofluorescence for T cells [CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3] and for macrophages [CD68, CD86, IRF5, MAF, and MRC1 (CD206)]. We used the inverse probability weighting method and the 4,465 incident cancer cases to adjust for selection bias.<h4>Results</h4>Immature desmoplastic reaction was associated with lower densities of intraepithelial CD3⁺CD8⁺CD45RO⁺ cells [multivariable odds ratio (OR) for the highest (vs. lowest) density category, 0.43; 95% confidence interval (CI), 0.29-0.62; P_trend <0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28-0.70; P_trend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3⁺CD8⁺CD45RO⁺ cells (P_trend <0.0001) and stromal M1-like macrophages (P_trend = 0.0007)] and for keloid-like collagen bundles (P_trend <0.0001 for intraepithelial CD3⁺CD8⁺CD45RO⁺ cells). In colorectal cancer-specific survival analyses, multivariable-adjusted hazard ratios (with 95% confidence intervals) were 0.32 (0.23-0.44; P_trend <0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16-0.39; P_trend <0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05-0.28; P_trend <0.0001) for absent (vs. marked) keloid-like collagen bundles.<h4>Conclusions</h4>Immature desmoplastic reaction and myxoid stroma were associated with lower densities of tumor intraepithelial memory cytotoxic T cells and stromal M1-like macrophages, likely reflecting interactions between tumor, immune, and stromal cells in the colorectal tumor microenvironment.Frontiers in immunologyDesmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer.PMC8980356R35 CA197735U01 CA167552P01 CA087969SU2C-AACR-DT22-17UM1 CA167552201860083, 201960541R35 CA253185R01 CA151993P01 CA055075R01 CA248857RSG NEC-130476P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, U01 CA167552, R35 CA253185 , R35 CA197735 , R01 CA151993 , R01 CA248857UM1 CA186107Wu KChan ATGiannakis MTwombly TSLau MCVayrynen JPUgai TKishikawa JArima KOgino SZhao MBorowsky JSong MZhong RTakashima YAkimoto NFujiyoshi KZhang XHaruki KMeyerhardt JANowak JAfalseDesmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer.<h4>Background</h4>The relationships between tumor stromal features (such as desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles) and immune cells in the colorectal carcinoma microenvironment have not yet been fully characterized.<h4>Methods</h4>In 908 tumors with available tissue among 4,465 incident colorectal adenocarcinoma cases in two prospective cohort studies, we examined desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles. We conducted multiplex immunofluorescence for T cells [CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3] and for macrophages [CD68, CD86, IRF5, MAF, and MRC1 (CD206)]. We used the inverse probability weighting method and the 4,465 incident cancer cases to adjust for selection bias.<h4>Results</h4>Immature desmoplastic reaction was associated with lower densities of intraepithelial CD3⁺CD8⁺CD45RO⁺ cells [multivariable odds ratio (OR) for the highest (vs. lowest) density category, 0.43; 95% confidence interval (CI), 0.29-0.62; P_trend <0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28-0.70; P_trend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3⁺CD8⁺CD45RO⁺ cells (P_trend <0.0001) and stromal M1-like macrophages (P_trend = 0.0007)] and for keloid-like collagen bundles (P_trend <0.0001 for intraepithelial CD3⁺CD8⁺CD45RO⁺ cells). In colorectal cancer-specific survival analyses, multivariable-adjusted hazard ratios (with 95% confidence intervals) were 0.32 (0.23-0.44; P_trend <0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16-0.39; P_trend <0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05-0.28; P_trend <0.0001) for absent (vs. marked) keloid-like collagen bundles.<h4>Conclusions</h4>Immature desmoplastic reaction and myxoid stroma were associated with lower densities of tumor intraepithelial memory cytotoxic T cells and stromal M1-like macrophages, likely reflecting interactions between tumor, immune, and stromal cells in the colorectal tumor microenvironment.2022-01-01T00:00:00Z20222026-03-18T13:40:38.821Z2025-04-04T12:57:44.483ZS-EPMC89803563539209210.3389/fimmu.2022.840198