PT - JOURNAL ARTICLE AU - Caio Abner Leite AU - Jose Mauricio Mota AU - Kalil Alves de Lima AU - Carlos Wagner Wanderley AU - Leticia Almeida Nascimento AU - Marcela Davoli Ferreira AU - Camila Meirelles Souza Silva AU - David Fernando Colon AU - Juliana Yumi Sakita AU - Vinicius Kannen AU - Paula Ramos Viacava AU - Maria Dirlei Begnami AU - Roberto Cesar Pereira Lima-Junior AU - Vladmir Claudio Cordeiro de Lima AU - Jose Carlos Alves-Filho AU - Fernando Queiroz Cunha AU - Ronaldo Albuquerque Ribeiro TI - Paradoxical interaction between cancer and long-term postsepsis disorder: impairment of de novo carcinogenesis versus favoring the growth of established tumors AID - 10.1136/jitc-2019-000129 DP - 2020 May 01 TA - Journal for ImmunoTherapy of Cancer PG - e000129 VI - 8 IP - 1 4099 - http://jitc.bmj.com/content/8/1/e000129.short 4100 - http://jitc.bmj.com/content/8/1/e000129.full SO - J Immunother Cancer2020 May 01; 8 AB - Background Previous data have reported that the growth of established tumors may be facilitated by postsepsis disorder through changes in the microenvironment and immune dysfunction. However, the influence of postsepsis disorder in initial carcinogenesis remains elusive.Methods In the present work, the effect of postsepsis on inflammation-induced early carcinogenesis was evaluated in an experimental model of colitis-associated colorectal cancer (CAC). We also analyzed the frequency and role of intestinal T regulatory cells (Treg) in CAC carcinogenesis.Results The colitis grade and the tumor development rate were evaluated postmortem or in vivo through serial colonoscopies. Sepsis-surviving mice (SSM) presented with a lower colonic DNA damage, polyp incidence, reduced tumor load, and milder colitis than their sham-operated counterparts. Ablating Treg led to restoration of the ability to develop colitis and tumor polyps in the SSM, in a similar fashion to that in the sham-operated mice. On the other hand, the growth of subcutaneously inoculated MC38luc colorectal cancer cells or previously established chemical CAC tumors was increased in SSM.Conclusion Our results provide evidence that postsepsis disorder has a dual effect in cancer development, inhibiting inflammation-induced early carcinogenesis in a Treg-dependent manner, while increasing the growth of previously established tumors.