Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group of T lymphocytes with the ability to suppress immune responses and maintain immune homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity and facilitate cancer progression by weakening functions of effector T cells (Teffs). Consequently, targeting Tregs to eliminate them from tumor microenvironments to improve Teffs’ activity could emerge as an effective strategy for cancer immunotherapy. This review outlines the biology of Tregs, detailing their origins, classification, and crucial markers. Our focus lies on the complex role of Tregs in cancer’s development, progression and treatment, particularly on their suppressive role upon antitumor responses via multiple mechanisms. We delve into Tregs’ involvement in immune checkpoint blockade (ICB) therapy, their dual effect on cancer immunotherapy and their potential biomarkers for ICB therapy effectiveness. We also summarize advances in the therapies that adjust Tregs to optimize ICB therapy, which may be crucial for devising innovative cancer treatment strategies.

Several epidemiological studies have identified diabetes as a risk factor for colorectal cancer (CRC). The potential pathophysiological mechanisms of this association include hyperinsulinemia, insulin-like growth factor (IGF) axis, hyperglycemia, inflammation induced by adipose tissue dysfunction, gastrointestinal motility disorder, and impaired immunological surveillance. Several studies have shown that underlying diabetes adversely affects the prognosis of patients with CRC. This review explores the novel anticancer agents targeting IGF-1R and receptor for advanced glycation end products (RAGE), both of which play a vital role in diabetes-induced colorectal tumorigenesis. Inhibitors of IGF-1R and RAGE are expected to become promising therapeutic choices, particularly for CRC patients with diabetes. Furthermore, hypoglycemic therapy is associated with the incidence of CRC. Selection of appropriate hypoglycemic agents, which can reduce the risk of CRC in diabetic patients, is an unmet issue. Therefore, this review mainly summarizes the current studies concerning the connections among diabetes, hypoglycemic therapy, and CRC as well as provides a synthesis of the underlying pathophysiological mechanisms. Our synthesis provides a theoretical basis for rational use of hypoglycemic therapies and early diagnosis and treatment of diabetes-related CRC.

During the last decades, several large randomized trials have demonstrated that neoadjuvant radiotherapy plays a well-established role in the improvement of locoregional control of rectal cancer but is not associated with increased long-term survival.^1-3 Therefore, the benefits and adverse events of radiotherapy should be carefully balanced when considering all potential effects of radiotherapy. Radiotherapy-associated second primary cancer (SPC) is a rare but notable late complication of cancer therapy.⁴

Doxorubicin (Dox), one of the most effective chemotherapy drug for cancer treatment, is limited by its severe side effects and chemoresistance. Dox induces DNA damage and leads to significant proteomic changes in the cancer cells, which makes the ubiquitin-proteasome system a potential target to enhance the efficacy of Dox therapy. The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features. In this preclinical study, we used eight human breast cancer cell lines, which represent the major molecular subtypes of breast cancer, to validate the cytotoxic effects of MLN9708, alone and in combination with Dox. We found that MLN9708 had cytotoxic effects, induced autophagy and MKP-1 expression, and enhanced Dox-induced apoptosis in these cell lines. MLN9708 also enhanced Dox-induced JNK and p38 phosphorylation and inhibited Dox-induced IκBα degradation. Our in vitro results suggest that MLN9708 has antitumor effects in breast cancer and can sensitize breast cancer cells to Dox treatment. This promising combination may be an effective and feasible therapeutic option for treating breast cancer and warrants clinical validation.

Natural orifice specimen extraction has been shown to reduce postoperative pain and wound complications, and provide better cosmetic outcome. However, whether transvaginal specimen extraction affects sexual function remains controversial. The purpose of this study was to investigate the short-term outcomes, sexual function, cosmetic outcomes and prognosis after colon cancer surgery with transvaginal specimen extraction. This study was a propensity score-matched comparative retrospective study, based on prospectively collected data in a single center. This study included 70 pairs of propensity score-matched female patients who underwent laparoscopic curative resection for stage I-III colon cancer with transvaginal specimen extraction and conventional specimen extraction between November 2015 and November 2020. Covariates used in the propensity score included age, tumor diameter, tumor differentiation, T stage and American Joint Committee on Cancer stage. Outcome measures included postoperative complication, postoperative sexual function, cosmetic result, disease-free survival and overall survival. Patients in transvaginal group were administered with less additional analgesics (P = 0.008), and had fewer wound complications (P = 0.028). None of patient in the two groups underwent anastomotic leakage, incisional disruption or vaginal fistula. The baseline pre-operative Female Sexual Function Index scores in two groups were the same, and no difference was found in postoperative score between the two groups (P = 0.790). The cosmetic score was significantly better in transvaginal group than that of conventional laparoscopy group (P = 0.000). During the follow-up period, there were no differences in OS or DFS between the two groups (P = 0.658, P = 0.663). Compared with laparoscopic colon cancer radical resection with specimen extraction, transvaginal specimen extraction is oncologically safe, brings better short-term outcomes, improved cosmetic results and has limited adverse effect on female's sexual function. This procedure can be further carried out in more appropriate patients.

Objective: This study aims to develop feasible nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of the local advanced rectal cancer (LARC) patients who were treated with neoadjuvant chemoradiotherapy (nCRT) and operation. Methods: A total of 243 LARC patients undergoing nCRT followed by total mesorectal excision (TME) were enrolled. Preoperative clinical features and postoperative pathological characteristics were collected. A Cox regression analysis was performed, and Cox-based nomograms were developed to predict the OS and CSS. We assessed the predictive performance of the nomogram with concordance index and calibration plots. Results: A total of 243 patients were included with a median follow-up period of 46 months (range from 9 to 86 months). Cox regression analysis showed that low BMI (BMI < 18.5, HR= 21.739, P < 0.05), high level of preoperative CA19-9 (HR = 3.369, P = 0.036), high ypStage (HR = 19.768, P < 0.001), positive neural invasion (HR = 4.218, P = 0.026) and no adjuvant chemotherapy (HR = 5.495, P < 0.001) were independent predictors of poor OS. Age ≥ 70 (HR = 2.284, P < 0.001), low BMI (BMI < 18.5, HR = 3.906, P < 0.05), positive preoperative CA19-9 (HR = 1.920, P = 0.012), high ypStage (HR = 5.147, P < 0.001) and positive neural invasion (HR = 2.873, P = 0.022) were independent predictors of poor CSS. The predictive nomograms were developed to predict the OS and CSS with a C-index of 0.837 and 0.760. Good statistical performance on internal validation was shown by calibration plots. Conclusion: In conclusion, this study demonstrated that BMI was an independent prognostic factor for OS and CSS in LARC patients treated with nCRT followed TME. A nomogram incorporating BMI, neural invasion, pre-CA19-9, ypStage, age, and adjuvant chemotherapy could be helpful to predict the OS and CSS.