Cigarette smoking and long-term incidence of colorectal cancer subclassified by tumor-infiltrating myeloid cells: A prospective cohort study

作者：Satoko Ugai, Hiroki Mizuno, Kosuke Matsuda, Atsushi Kondo, Yuxue Zhong, Nobuhiro Nakazawa, Satoshi Miyahara, Naoka Murakami, Sara A. Väyrynen, Andrew T. Chan, Mingyang Song, Marios Giannakis, Jeffrey A. Meyerhardt, Juha P. Väyrynen, Jonathan Andrew Nowak, Shuji Ogino, Tomotaka Ugai · 发表于：Environmental Pollution · 年份：2026 · DOI：10.1016/j.envpol.2026.128220 · 被引用次数：1 · 研究领域：Immune cells in cancer、Inflammatory Biomarkers in Disease Prognosis、Multiple and Secondary Primary Cancers

Evidence indicates that cigarette smoking affects anti-tumor immunity. We tested a hypothesis that the association of smoking with long-term colorectal cancer (CRC) incidence might differ by myeloid cell infiltrates in tumors, which may play roles in cancer immune evasion. We utilized the prospective cohort incident-tumor biobank method on two longitudinal prospective cohort studies, namely the Nurses’ Health Study and the Health Professionals Follow-up Study. To identify myeloid cells in the tumor microenvironment, we applied multiplexed immunofluorescence (for ARG1, CD14, CD15, CD33, HLA-DR, and KRT) combined with digital image analysis and machine learning. We examined the association of smoking with long-term incidence of CRC subclassified by myeloid cell densities using the multivariable inverse-probability-weighted duplication-method Cox regression model. During the follow-up of 131,143 cohort participants (3,647,434 person-years), we documented 3092 incident CRC cases, including 854 cases with available data on tissue myeloid cells. The association of pack-years smoked with long-term CRC incidence differed by intraepithelial CD14 + HLA-DR - cell densities (P heterogeneity <0.001) but not by CD15 + cell densities (P heterogeneity = 0.32). Smoking pack-years were strongly associated with the incidence of tumors with high CD14 + HLA-DR - cell densities (multivariable HR for ≥40 vs. 0 pack-years, 1.86; 95% CI, 1.35-2.57; P trend <0.001) but not with that of tumors with int...