title: Leukocyte populations and IL-6 in the tumor microenvironment of an orthotopic colorectal cancer model.
abstract: Colorectal cancer (CRC) is a major health problem worldwide. It is often diagnosed late due to its asymptomatic nature. As with all cancers, an immune reaction is involved; however, in CRC, it is unknown if this immune response is favorable or unfavorable for disease progression. In this study, the immune response in mesenteric lymph nodes (MLNs) and Peyer's patches was investigated during development of CRC in an orthotopic mouse model. CRC was induced by injecting CT26 cells into the cecum wall of BALB/c mice. Flow cytometry was used to analyze leukocyte populations involved in tumor immunity in MLNs and Peyer's patches. Cryostat sections for immunohistochemistry were prepared from the caecum and colon from CRC-induced and sham-operated animals. Cytokines produced by mouse CT26 cell line were measuredin vitroandin vivo Significant increases in the number of CD8(+)/TCR(+)and CD49b(+)/TCR(-)(natural killer) cells were found in MLNs and Peyer's patches in the CRC group. In addition, γδT cells were present in the lamina propria of the colon tissues from sham-operated mice, but absent in the colon tissues from mice with CRC. Immunohistochemical analysis of tumorous tissues showed eosinophil, CD69(+)T cell, and CD11b(+)cell infiltration. Bothin vitroandin vivoCT26 tumor cells were interleukin (IL)-6 positive. In addition, tumor-infiltrating CD45(+)cells were also IL-6 positive. In summary, the kinetics of the immune response to CRC and the key effector lymphocytes that are implicated in tumor immunity are demonstrated. Furthermore, IL-6 is a key cytokine present within the tumor microenvironment.
authors.affiliation: Centre for Chronic Diseases, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Miller
authors.affiliation: North West Academic Centre, University of Melbourne and Western Health, Sunshine Hospital, St Albans, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Senior
authors.affiliation: Centre for Chronic Diseases, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Monica
authors.initials: M
authors.lastname: Prakash
authors.affiliation: Centre for Chronic Diseases, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.affiliation: Centre for Chronic Diseases, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Samy
authors.initials: S
authors.lastname: Sakkal
authors.affiliation: Centre for Chronic Diseases, College of Health and Biomedicine, Victoria University, Melbourne, Australia kulmira.nurgali@vu.edu.au.
authors.forename: Kulmira
authors.initials: K
authors.lastname: Nurgali
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines; D015850:Interleukin-6
keywords: IL-6; Peyer's patches; colorectal cancer; immune system; mesenteric lymph nodes