Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction

Fujiyoshi, Kenji; Chen, Yang; Haruki, Koichiro; Ugai, Tomotaka; Kishikawa, Junko; Hamada, Tsuyoshi; Liu, Li; Arima, Kei; Borowsky, Jennifer; Väyrynen, Juha P.; Zhao, Melissa; Lau, Mai Chan; Gu, Simeng; Shi, Shanshan; Akimoto, Naohiko; Twombly, Tyler S.; Drew, David A.; Song, Mingyang; Chan, Andrew T.; Giovannucci, Edward; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Nishihara, Reiko; Lennerz, Jochen K.; Giannakis, Marios; Nowak, Jonathan A.; Zhang, Xuehong; Wu, Kana; Ogino, Shuji

doi:10.1093/jncics/pkaa040

Cited by 9 publications

(9 citation statements)

References 60 publications

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“…Our results, along with another recent study in HPV(−) HNSCC, suggest that the immunosuppressive effect of tobacco use at the time of diagnosis may be a feature shared by HNSCC tumors regardless of HPV status ( Iglesia et al., 2020 ). Beyond SCC, tobacco has been associated with immunosuppression in primary colorectal carcinoma, another highly immunogenic tumor ( Hamada et al., 2018 ; Fujiyoshi et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer

et al. 2022

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“…39 Beyond SCC, tobacco has been associated with immunosuppression in primary colorectal carcinoma, another highly immunogenic tumor. 40,41 Further, tobacco exposure influences HPV-specific immune responses. Multiple groups have demonstrated that tobacco use is associated with impaired immune responses and clearance of oncogenic HPV infections in human female genital infections.…”

Section: Discussionmentioning

confidence: 99%

“…39 Beyond SCC, tobacco has been associated with immunosuppression in primary colorectal carcinoma, another highly immunogenic tumor. 40,41…”

Section: Discussionmentioning

confidence: 99%

Comparative Multiomic Analysis Reveals Low T Cell Infiltration as the Primary Feature of Tobacco Use in HPV(+) Oropharyngeal Cancer

Wahle

Zolkind²,

Ramirez³

et al. 2021

Preprint

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Purpose: Tobacco use is an independent adverse prognostic feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Despite this, the biologic features associated with tobacco use have not been systematically investigated in this population. We sought to characterize the genomic and immunologic features of HPV(+) OPSCC associated with tobacco use and adverse oncologic outcomes. Experimental Design: Whole exome sequencing of 47 primary HPV(+) OPSCC tumors was performed to investigate mutational differences associated with tobacco exposure. To characterize the tumor immune microenvironment (TIME), targeted mRNA hybridization was performed and immunohistochemical (IHC) staining was used to validate these findings. Results: Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at the time of diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T>C substitutions and a lower proportion of mutational signatures typically observed in HPV(+) OPSCC tumors, but was not associated with increases in mutational burden or the rate of recurrent oncogenic mutations. Conclusions: In HPV(+) OPSCC, low T cell infiltration of primary tumors is associated with current tobacco use and worse oncologic outcomes. Rather than an increased mutational burden, tobacco's primary and clinically relevant association is immunosuppression of the primary TIME. An objective clinical assay like the TGEP, which quantifies immune infiltration of the primary TIME, may have value for HPV(+) OPSCC risk stratification in future clinical trials.

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“…Integrative MPE research strategies are needed to address this research gap. Previous studies have suggested differential effects of aspirin use, vitamin D level, physical activity, cigarette smoking and coffee intake on clinical outcomes of patients with CRC by levels of lymphocytic reaction or tumour CD274 (PD-L1) expression 85 182–185. Investigations of the effects of modifiable exposures on clinical outcomes and underlying mechanisms (presumably through microbiota and immunity) can have substantial implications in the development of precision medicine.…”

Section: Tumour Microenvironmentmentioning

confidence: 99%

Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science

Inamura

Hamada

Bullman

et al. 2022

Gut

Self Cite

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Cancer is generally regarded as a localised disease, with the well-established role of the tumour microenvironment. However, the realm of cancer goes beyond the tumour microenvironment, and cancer should also be regarded as a systemic and environmental disease. The exposome (ie, the totality of exposures), which encompasses diets, supplements, smoking, alcohol, other lifestyle factors, medications, etc, likely alters the microbiome (inclusive of bacteria, viruses, archaea, fungi, parasites, etc) and immune system in various body sites and influences tumour phenotypes. The systemic metabolic/inflammatory status, which is likely influenced by exposures and intestinal physiological changes, may affect tissue microenvironment of colorectum and any other organs. Germline genomic factors can modify disease phenotypes via gene-by-environment interactions. Although challenges exist, it is crucial to advance not only basic experimental research that can analyse the effects of exposures, microorganisms and microenvironmental components on tumour evolution but also interdisciplinary human population research that can dissect the complex pathogenic roles of the exposome, microbiome and immunome. Metagenomic, metatranscriptomic and metabolomic analyses should be integrated into well-designed population research combined with advanced methodologies of artificial intelligence and molecular pathological epidemiology. Ideally, a prospective cohort study design that enables biospecimen (such as stool) collection before disease detection should be considered to address reverse causation and recall biases. Robust experimental and observational research together can provide insights into dynamic interactions between environmental exposures, microbiota, tumour and immunity during carcinogenesis processes, thereby helping us develop precision prevention and therapeutic strategies to ultimately reduce the cancer burden.

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Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction

Cited by 9 publications

References 60 publications

Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer

Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer

Comparative Multiomic Analysis Reveals Low T Cell Infiltration as the Primary Feature of Tobacco Use in HPV(+) Oropharyngeal Cancer

Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science

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