Background Distant metastasis is the major cause of mortality in patients with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy. Local radiotherapy can trigger an abscopal response to metastatic tumor cells. However, the abscopal effect is a rare event. CD4+ regulatory T (Treg) cell is a highly immune-suppressive subset which impedes immune surveillance against cancer, prevents the development of effective antitumor immunity and promotes tumor progression. We assume that the exploitation of the proimmunogenic effects of radiotherapy with anti-CD25 or anti-Cytotoxic T-Lymphocyte Associated Protein 4 (anti-CTLA4) monoclonal antibodies (mAbs) may enhance the local and abscopal effects in rectal cancer and improve the therapeutic outcome. Methods mRNA expression profiling of 81 pretreatment biopsy samples from LARC patients who received neoadjuvant radiotherapy (nRT) was performed to analyze the correlation between gene expression and prognosis. A retrospective analysis of patients with rectal cancer with distant metastasis or synchronous extracolonic cancers was performed to evaluate the abscopal effect of radiotherapy on rectal cancer. Two different dual-tumor mouse models were established to investigate the efficacy of single dose and dose-fractionated radiotherapy combined with anti-CD25 or anti-CTLA4 and anti-Programmed cell death 1 ligand 1 (anti-PD1) mAbs on the local tumor growth and liver metastasis. The univariate Cox regression analysis, one-way analysis of variance, Dunnett’s test, a mixed-effect linear model and Kaplan-Meier survival analysis were used to calculate p values. Results The proportion of Tregs in pre-nRT biopsies was negatively correlated with prognosis (p=0.007). The retrospective analysis showed that regressing liver metastases were infiltrated by CD8+ T cells. In contrast, stable/progressing metastases and synchronous extracolonic cancers were characterized by PD1+ T cells and Tregs infiltration. Animal experiment results demonstrated that the combination of radiotherapy and anti-CD25/CTLA4 mAb resulted in a significant increase in CD8+ T cells and CD8+/CD4+ ratio in primary and secondary tumors compared with the irradiation alone group (all p<0.05 or p<0.01). The combined treatment was able to decrease Tregs, PD1+CD8+ and PD1+CD4+ T cells (p<0.05), suppress locally irradiated and distal unirradiated tumor growth, and improve overall survival rate. Radiotherapy in conjunction with anti-CTLA4 reduced liver metastasis (p<0.05). Conclusions These data indicated that radiotherapy plus depletion of Tregs was able to improve the antitumor response and generate an abscopal effect.

Given the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer. Colorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models. miR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and β-catenin, while enhanced the mesenchymal markers vimentin. Our data demonstrate that miR-181a expression is associated with CRC liver metastasis and survival. miR-181a has strong tumor-promoting effects through inhibiting the expression of WIF-1, and its potential role in promoting epithelial-mesenchymal transition.

In China, colorectal cancer (CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first worldwide in the number of new CRC cases and CRC-related deaths because of its comparatively large population. This disease represents a threat to the health of population and incurs a heavy economic burden on the society and individuals. CRC has various risk factors, including age, sex, lifestyle, genetic factors, obesity, diabetes, gut microbiota status, and precancerous lesions. Furthermore, incidence and mortality rates of CRC are closely related to socioeconomic development levels, varying according to regional and population characteristics. Prevention is the main strategy to reduce incidence and mortality rates of CRC. This can be achieved through strategies stimulating lifestyle changes, healthy diet habits, and early screening for high-risk individuals. To reduce the burden of CRC, public health officials should promote prevention and management of modifiable risk factors through national policies. The rising incidence and mortality rates of CRC in China may be timely curbed by clarifying specific epidemiological characteristics, optimizing early screening strategies, and strictly implementing diagnosis and treatment guidelines. Thus, this study aimed to collect and report the current research status on epidemiology and risk factors of CRC in China.

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

Changing patterns of colorectal cancer in China over a period of 20 years

Mucinous adenocarcinoma: A unique clinicopathological subtype in colorectal cancer