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

Résumé fourni par la source

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 intermediate or low CD14 + HLA-DR - cell densities (P trend ≥0.1). These differential associations generally persisted in non-microsatellite instability-high tumors. In conclusion, the association of smoking with long-term CRC incidence was stronger for tumors with more abundant CD14 + HLA-DR - immature monocytes, highlighting the interplay of smoking and immature monocytic myeloid cells in colorectal tumorigenesis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.