Cancer occurrence in patients with inflammatory bowel disease in treatment with anti-TNF: report of three cases and literature review

Amaral, Lucas Camargo Gamba Martins do; Correa, Luiz Henrique Locks; Accord, Cassiano Coral; Santos, Thamy dos; Kock, Beatriz de Oliveira; Kock, Kaiser de Souza

doi:10.5935/2526-8732.20200042

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“…Recent observational studies have reported negatively on the increased risk of promotion of malignancy in patients using anti-TNFα mAb [ 4 – 6 ]. In contrast, as sporadic reports of tumor growth during anti-TNFα mAb use have been published [ 7 , 8 ], the possibility that anti-TNFα mAb use may influence tumor growth cannot be ruled out.…”

Section: Introductionmentioning

confidence: 98%

Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model

et al. 2023

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The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated macrophages. Anti-TNFα mAb acts as an inhibitor of tumor progression in the tumor microenvironment of a colorectal cancer orthotopic transplant mouse model.

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