Tumor-specific CD8+T cells are exposed to persistent antigenic stimulation which induces a dysfunctional state called “exhaustion.” Though functioning to limit damage caused by immune response, T cell exhaustion leads to attenuated effector function whereby cytotoxic CD8+T cells fail to control tumor progression in the late stage. This pathway is a dynamic process from activation to “progenitor exhaustion” through to “terminally exhaustion” with distinct properties. With the rapid development of immunotherapy via enhancing T cell function, new studies are dissecting the mechanisms and identifying specific biomarkers of dynamic differentiation during the process of exhaustion. Further, although immune checkpoint inhibitors (ICIs) have achieved great success in clinical practice, most patients still show limited efficacy to ICIs. The expansion and differentiation of progenitor exhausted T cells explained the success of ICIs while the depletion of the progenitor T cell pool and the transient effector function of terminally exhausted T cells accounted for the failure of immune monotherapy in the context of exorbitant tumor burden. Thus, combination strategies are urgent to be utilized based on the reduction of tumor burden or the expansion of the progenitor T cell pool. In this review, we aim to introduce the concept of homeostasis of the activated and exhausted status of CD8+T cells in the tumor immune microenvironment, and present recent findings on dynamic differentiation process during T cell exhaustion and the implications for combination strategies in immune therapy.
Human guts harbor abundant microbes that regulate many aspects of host physiology. However, bacterial imbalance or dysbiosis in the gut due to the dietary or environmental changes may cause colorectal cancer (CRC). Increasing studies show that gut microbiota plays an important role in the occurrence and development of CRC, as a result of virulence factors, bacterial metabolites, or inflammatory pathways. In the future, probiotics or targeting the microbiota will probably be a powerful weapon in the battle against CRC. This review seeks to outline the relationship between gut microbiota and the development of CRC as well as the potential mechanisms of microbiota involved in treatment of CRC, so as to provide some references for research on the development, prevention, and treatment of this disease.
Numerous studies have revealed that the gut microbiota serves an important role in the pathogenesis of colorectal cancer (CRC). The present study aimed to investigate the populations present in the gut microbiota in patients with CRC of different stages and at different sites. Fecal samples were obtained from 67 CRC patients and 30 healthy controls, which were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Increased diversity of the fecal gut microbiota in patients with CRC was reported compared with the healthy controls. In the present study, at the genus level, the relative abundances of Prevotella, Collinsella and Peptostreptococcus in the gut microbiota of CRC patients were substantially increased compared with healthy controls, while the relative abundance of Escherichia-Shigella was significantly lower. In addition, differences in the fecal gut microbiota were also compared between patients with stage I–IV CRC and healthy controls. The results revealed that the abundances of the genera Peptostreptococcus, Collinsella and Ruminococcus were significantly increased in patients with CRC stage I compared with the healthy controls, while Alistipes was enriched in patients with stage III CRC compared with patients with stage IV. Furthermore, the present study reported that the genera Veillonella and Coprobacter were more abundant in the proximal segments than in the distal segments of the colon. In conclusion, despite the low number of samples employed in the present study, a signature of genera indicating dysbiosis of the gut microbiota of patients with stage I–IV CRC patients was proposed, which may provide insight into the mechanisms underlying the progression of CRC. These findings are also valuable for developing novel fecal diagnostic methods and therapeutic strategies for the treatment of CRC.
PurposeTo demonstrate the feasibility, safety, and technical strategies of hand-assisted laparoscopic complete mesocolic excision (HAL-CME) and to compare oncological outcomes between HAL-CME and the open approach (O-CME) for right colon cancers.MethodsPatients who were scheduled to undergo a right hemicolectomy were divided into HAL-CME and O-CME groups. Measured outcomes included demographic variables, perioperative parameters, and follow-up data. Demographic variables included age, sex distribution, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, previous abdominal surgery, tumor localization, and potential comorbidities. Perioperative parameters included incision length, operative time, blood loss, conversion rate, postoperative pain score, postoperative first passage of flatus, duration of hospital stay, total cost, number of lymph nodes retrieved, TNM classification, and postoperative complications. Follow-up data included follow-up time, use of chemotherapy, local recurrence rate, distant metastasis rate, and short-term survival rate.ResultsIn total, 150 patients (HAL-CME, 78; O-CME, 72) were included. The groups were similar in age, sex distribution, BMI, ASA classification, history of previous abdominal surgeries, tumor localization, and potential comorbidities. Patients in the HAL-CME group had shorter incision lengths, longer operative times, less operative blood loss, lower pain scores, earlier first passage of flatus, shorter hospital stay, higher total costs, similar numbers of lymph nodes retrieved, similar TNM classifications, and a comparable incidence of postoperative complications. The 2 groups were also similar in local recurrence rate, distant metastasis rate, and short-term survival rate.ConclusionThe results demonstrate that the HAL-CME procedure is a safe, valid, and feasible surgical method for right hemicolon cancers.
Background: To understand the biological effect of gut microbiome on the progression of colorectal cancer (CRC), we sequenced the V3-V4 region of the 16S rRNA gene to illustrate the overall structure of microbiota in the CRC patients. Methods: In this study, a total of 66 CRC patients were dichotomized into different groups based on the following characteristics: paired tumor and adjacent normal tissues, distal and proximal CRC segments, MMR (-) and MMR (+), different TNM staging and clinic tumor staging. Results: By sequencing and comparing the microbial assemblages, our results indicated that 7 microbe genus (Fusobacterium, Faecalibacterium, Akkermansia, Ruminococcus2, Parabacteroides, Streptococcus, and f_Ruminococcaceae) were significantly different between tumor and adjacent normal tissues; and 5 microbe genus (Bacteroides, Fusobacterium, Faecalibacterium, Parabacteroides, and Ruminococcus2) were significantly different between distal and proximal CRC segments; only 2 microbe genus (f_Enterobacteriaceae and Granulicatella) were significantly different between MMR (-) and MMR (+); but there was no significant microbial difference were detected neither in the TNM staging nor in the clinic tumor staging. Conclusion: All these findings implied a better understanding of the alteration in the gut microbiome, which may offer new insight into diagnosing and therapying for CRC patients.
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