Colibactin-positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer.

Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in the APCMin/+ mice colon. T-cell density was evaluated by immunohistochemistry in human tumors known for their CoPEC status. APCmin/+ mice were chronically infected with a CoPEC strain (11G5). Immune cells (neutrophils and T-cell populations) were then quantified by immunofluorescent staining of the colon. The quantification of lymphoid populations was also performed in the mesenteric lymph nodes (MLNs). Here, we show that the colonization of CRC patients by CoPEC is associated with a decrease of tumor-infiltrating T lymphocytes (CD3+ T-cells). Similarly, we demonstrated, in mice, that CoPEC chronic infection decreases CD3+ and CD8+ T-cells and increases colonic inflammation. In addition, we noticed a significant decrease in antitumor T-cells in the MLNs of CoPEC-infected mice compared to that of controls. Moreover, we show that CoPEC infection decreases the antimouse PD-1 immunotherapy efficacy in MC38 tumor model. Our findings suggest that CoPEC could promote a procarcinogenic immune environment through impairment of antitumor T-cell response, leading to tumoral resistance to immunotherapy. CoPEC could thus be a new biomarker predicting the anti-PD-1 response in CRC.

Growth hormone receptor expression in atrophying muscle fibers of rats.

Biological actions of GH on muscle growth and metabolism are mediated through specific trans-membrane receptors. The aim of this study was to determine GH receptor (GHR) mRNA expression in muscle atrophy. GHR gene expression in the rat was investigated by in situ hybridization and RT-PCR in slow-twitch oxidative muscle [soleus (SOL)] and fast-twitch glycolytic muscle [extensor digitorum longus (EDL)] after 7 and 35 d of hindlimb unloading. In control rats, the RT-PCR mRNAs levels of GHR were greater (+34%) in EDL compared with SOL. At single fiber level, relative expression of GHR mRNA increases in the following order: IIb>IIa>I. After hindlimb unloading, GHR expression significantly increased in atrophied SOL muscle after 7 (+170%) and 35 (+220%) d, whereas no significant alterations appeared in the EDL muscle. At the individual fiber level, in situ hybridization demonstrated this increase was accounted for by an increase in type I fiber expression of GHR transcripts. This increase was also seen in the EDL, but the low content of type I fibers in EDL resulted in a nonsignificant increase in GHR transcript content. The present data suggest that muscle atrophy is associated with a muscle fiber type-specific GHR mRNA up-regulation mechanism that helps protect atrophying fibers in EDL but might be part of an attempt to repair in SOL.