Paradoxical interaction between cancer and long-term postsepsis disorder: impairment of de novo carcinogenesis versus favoring the growth of established tumors.

Published on May 1, 2020in Journal for ImmunoTherapy of Cancer9.913
· DOI :10.1136/JITC-2019-000129
Caio Abner Leite12
Estimated H-index: 12
Jose Mauricio Mota16
Estimated H-index: 16
(USP: University of São Paulo)
+ 14 AuthorsRonaldo A. Ribeiro57
Estimated H-index: 57
(UFC: Federal University of Ceará)
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.
📖 Papers frequently viewed together
8 Authors (Kevin G. Leong, ..., Ana Krtolica)
13 Citations
13 Citations
#1Juliana Yumi Sakita (USP: University of São Paulo)H-Index: 5
#2Michael Bader (Charité)H-Index: 117
Last. Vinicius Kannen (USP: University of São Paulo)H-Index: 10
view all 19 authors...
: Serotonin (5-HT) signaling pathways are thought to be involved in colorectal tumorigenesis (CRT), but the role of 5-HT synthesis in the early steps of this process is presently unknown. In this study, we used carcinogen treatment in the tryptophan hydroxylase 1 knockout (Tph1KO) and transgenic (Tph1fl/fl VillinCre ) mouse models defective in 5-HT synthesis to investigate the early mutagenic events associated with CRT. Our observations of the colonic crypt post-treatment followed a timeline des...
11 CitationsSource
#1Adrian Frick (Medical University of Vienna)H-Index: 4
#2Vineeta Khare (Medical University of Vienna)H-Index: 15
Last. Christoph Gasche (Medical University of Vienna)H-Index: 56
view all 9 authors...
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated-cancer (CAC); however, the underlying processes of disease progression are not completely understood. Here, the molecular processes of inflammation-driven colon carcinogenesis were investigated using IL10-deficient mice (IL10 KO). IL10 KO mice were euthanized after development of colitis and dysplasia. IHC was performed for markers of colitis-induced DNA damage (CIDD): oxidative DNA lesions (8-oxoG...
21 CitationsSource
#1Koji Taniguchi (Kyushu University)H-Index: 31
#2Michael Karin (UCSD: University of California, San Diego)H-Index: 257
Here, Koji Taniguchi and Michael Karin discuss the key roles of the nuclear factor-κB (NF-κB) transcription factor in cancer-related inflammation and consider the potential of targeting NF-κB in different types of cancer.
774 CitationsSource
#1Hallie C. Prescott (UM: University of Michigan)H-Index: 27
#2Derek C. Angus (University of Pittsburgh)H-Index: 128
Importance Survival from sepsis has improved in recent years, resulting in an increasing number of patients who have survived sepsis treatment. Current sepsis guidelines do not provide guidance on posthospital care or recovery. Observations Each year, more than 19 million individuals develop sepsis, defined as a life-threatening acute organ dysfunction secondary to infection. Approximately 14 million survive to hospital discharge and their prognosis varies. Half of patients recover, one-third di...
260 CitationsSource
#1Marcela Rodrigues de Camargo (UNESP: Sao Paulo State University)H-Index: 1
#2Carolina Mendonça Gorgulho (UNESP: Sao Paulo State University)H-Index: 5
Last. Ramon Kaneno (UNESP: Sao Paulo State University)H-Index: 16
view all 7 authors...
Abstract Aim: Considering the central role of dendritic cells (DCs) on the development of an antitumor immune response, in this study we used a murine model to evaluate how DC transfection with drug-treated tumor cell RNA changes their phenotype, and whether transfection enhances the in vivo effectiveness of a DC-based antitumor vaccine. Materials and Methods: MC-38 colorectal tumor cells were pretreated with the minimum effective concentration of 5-fluorouracil (5-FU), then their total RNA was ...
1 CitationsSource
#1Chengxin Luo (Sichuan University)H-Index: 5
#2Hu Zhang (Sichuan University)H-Index: 14
Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC). The risk factors of CRC in IBD patients include long disease duration, extensive colitis, severe histological inflammation, and coexistence with primary sclerosing cholangitis (PSC). Several molecular pathways that contribute to sporadic CRC are also involved in the pathogenesis of colitis-associated CRC. It is well established that long-standing chronic inflammation is a key predisposi...
60 CitationsSource
#1Daniele C. Nascimento (USP: University of São Paulo)H-Index: 16
#2Paulo H. Melo (USP: University of São Paulo)H-Index: 6
Last. José C. Alves-Filho (USP: University of São Paulo)H-Index: 47
view all 15 authors...
Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury...
98 CitationsSource
#1Cho-Rong Lee (Gwangju Institute of Science and Technology)H-Index: 6
#2Yewon Kwak (Gwangju Institute of Science and Technology)H-Index: 2
Last. Sung-Gyoo Park (Gwangju Institute of Science and Technology)H-Index: 25
view all 12 authors...
Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth...
62 CitationsSource
#1Belal Chaudhary (University of Cambridge)H-Index: 9
#2Eyad ElkordH-Index: 31
Recent years have seen significant efforts in understanding and modulating the immune response in cancer. In this context, immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have come under intense investigation for their proposed roles in suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment, thus enabling tumor immune evasion. Additionally, recent evidence indicates that Tregs comprise d...
272 CitationsSource
#1Yin Cao (Harvard University)H-Index: 31
#2Reiko NishiharaH-Index: 50
Last. Andrew T. Chan (Harvard University)H-Index: 110
view all 10 authors...
Importance The US Preventive Services Task Force recently recommended the use of aspirin to prevent colorectal cancer and cardiovascular disease among many US adults. However, the association of aspirin use with the risk for other cancer types and the potential population-wide effect of aspirin use on cancer, particularly within the context of screening, remain uncertain. Objectives To examine the potential benefits of aspirin use for overall and subtype-specific cancer prevention at a range of ...
183 CitationsSource
Cited By1
#1Chong Zeng (Southern Medical University)
Last. Feiyue Xing (JNU: Jinan University)H-Index: 12
view all 5 authors...