An ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating “hot” versus “cold” tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple ‘-omic’ approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi “-omic” approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.

Little is known of the patterns of expression of ACE2 and TMPRSS2 or the clinical characteristics of COVID-19 in patients with COVID-19 and colorectal cancer. We found in both bulk and single-cell RNA-seq profiles that ACE2 and TMPRSS2 were expressed at high levels on tumor and normal colorectal epithelial tissues. Clinically, patients with colorectal cancer and COVID-19 were more likely to have lymphopenia, higher respiratory rate, and high hypersensitive C-reactive protein levels than matched patients with COVID-19 but without cancer. These results suggest that patients with colorectal cancer may be particularly susceptible to SARS-CoV-2 infection. Further mechanistic studies are needed to support our findings.

The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. We aimed to investigate the correlation between the decrease in peripheral blood lymphocytes during radiotherapy (RT) and the spleen irradiation dose in patients with hepatocellular carcinoma (HCC). The subjects were 59 patients with HCC who had received RT from 2005 to 2014. The Min ALC (minimum value of absolute counts for peripheral blood lymphocytes) was collected from the routine workup for each patient prior to RT and weekly during RT. Spleen dose-volume variables, including the percentage of the organ volume receiving ≥ n Gy (Vn) and the mean spleen dose (MSD), were calculated using Eclipse treatment planning. Potential associations between dosimetric variables and the Min ALC were assessed by multiple linear regression analysis. Peripheral lymphocytes decreased during RT (P < 0.001). The Min ALC correlated with the MSD (P = 0.005), spleen V5 (P = 0.001), spleen V25 (P = 0.026) and spleen V30 (P = 0.018). Controlling for the Karnofsky performance status (KPS), sex, age, Child-Pugh grade, total dose and tumour stage, a multiple linear regression model with bootstrap analysis of 1000 replicates showed that only the spleen V5 was correlated with the decrease in the Min ALC (P < 0.05). According to the receiver-operating characteristic (ROC) curve analysis, the predictive cutoff values of the MSD, V5, V25 and V30 of the spleen for the Min ALC were 227.72 cGy, 17.84, 0.98 and 0.42%, respectively (P = 0.002, P = 0.004, P = 0.007 and P = 0.002, respectively). Furthermore, an MSD ≥ 227.72 cGy (OR = 14.39; 95% CI, 12.18 to 16.60) and V5 (OR = 7.99; 95% CI, 6.91 to 9.07) of the spleen significantly predicted the Min ALC. Higher spleen irradiation doses were significantly correlated with lower Min ALC during RT for HCC. V5 should be limited in clinical practice. Maximum sparing for spleen irradiation during RT is recommended to preserve peripheral blood lymphocytes, which may decrease immunosuppression.

Purpose: We sought to examine the role of pretreatment systemic immune-inflammation index (SII) in hormone receptor-negative, human epidermal growth factor receptor 2+ (HER2+) breast cancer patients. Patients and methods: 155 HER2+ patients treated in our hospital from September 3, 2002, to September 21, 2012, were retrospectively enrolled. SII was established as neutrophil x platelet/lymphocyte counts. The median value of SII was used as cut-off value. We used the Kaplan-Meier method to evaluate the overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS). To comparatively evaluate the survival rates between patients from two groups, we used the log-rank test. For identifying independent factors of prognosis, we used the Cox regression model, applying multivariate statistics. Results: Analyses show that HER2+ patients with high and low SII had median DFS of 15.1 and 31.5 months, respectively (P<0.001), while the median DMFS in HER2+ patients with high SII was 18.4 and in patients with low SII was 33.0 months (P=0.001), and the median OS were 54.5 and 71.1 months respectively in high and low SII patients, respectively (P=0.002). Multivariate analysis had revealed increased SII independently linked to poor DFS (HR =1.46, 95% CI: 1.01–2.11, P=0.045). The difference between SII and DMFS bore no statistical significance. (HR =1.40, 95% CI: 0.96–2.03, P=0.078), while high SII independently predicted short OS (HR =1.51, 95% CI: 1.02–2.25, P=0.038). Conclusion: Our findings suggest that increased SII independently predicts poor survival for hormone receptor-negative, HER2+ breast cancer patients. Prospective studies are, however, required to confirm the role of SII in the prognosis of patients with HER2+ before clinical use.

Chondrosarcomas are a heterogeneous group of malignant bone tumors that produce hyaline cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers, including conventional and dedifferentiated chondrosarcomas. These mutations lead to the inability of IDH to convert isocitrate into α-ketoglutarate (α-KG). Instead, α-KG is reduced into D-2-hydroxyglutarate (D-2HG), an oncometabolite. IDH mutations and D-2HG are thought to contribute to tumorigenesis due to the role of D-2HG as a competitive inhibitor of α-KG-dependent dioxygenases. However, the function of IDH mutations in chondrosarcomas has not been clearly defined. In this study, we knocked out mutant IDH1 (IDH1^mut) in two chondrosarcoma cell lines using the CRISPR/Cas9 system. We observed that D-2HG production, anchorage-independent growth, and cell migration were significantly suppressed in the IDH1^mut knockout cells. Loss of IDH1^mut also led to a marked attenuation of chondrosarcoma formation and D-2HG production in a xenograft model. In addition, RNA-Seq analysis of IDH1^mut knockout cells revealed downregulation of several integrin genes, including those of integrin alpha 5 (ITGA5) and integrin beta 5 (ITGB5). We further demonstrated that deregulation of integrin-mediated processes contributed to the tumorigenicity of IDH1-mutant chondrosarcoma cells. Our findings showed that IDH1^mut knockout abrogates chondrosarcoma genesis through modulation of integrins. This suggests that integrin molecules are appealing candidates for combinatorial regimens with IDH1^mut inhibitors for chondrosarcomas that harbor this mutation.

Further analysis of phase I trial of the KEYNOTE-001 has shown that previous radiotherapy improves the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab treatment, possibly explained by the radiation-induced specific anti-cancer immunity with a memory effect. In this study, we aimed to investigate the peripheral memory and naïve T cells as predictors of early response in lung metastases post-stereotactic body radiotherapy (SBRT). Sixty-six lung metastases patients with NSCLC who received SBRT were enrolled in this study. Analyses of peripheral memory CD4+ T, memory CD8+ T, naive CD4+ T, and naive CD8+ T in NSCLC patients were performed by flow cytometry. Evaluations of the link between immune cells and early radiation response a month after SBRT were carried out via logistic regression analyses. Higher levels of memory CD4+ T, memory CD8+ T, and lower levels of naïve CD4+ T, CD4+ naïve/memory ratio, and CD8+ naïve/memory ratio were shown in responders compared with non-responders (all P < 0.05). Logistic regression analyses of univariate and multivariate revealed that peripheral memory CD4+ T (OR: 0.14, 95% CI 0.04–0.50, P = 0.003; OR: 0.17, 95% CI 0.05–0.66, P = 0.010), memory CD8+ T (OR: 0.11, 95% CI 0.01–0.87, P = 0.037; OR: 0.11, 95% CI 0.01–0.97, P = 0.047), naïve CD4+ T (OR: 16.25, 95% CI 3.17–83.13, P = 0.001; OR: 12.67, 95% CI 2.26–71.18, P = 0.004) and CD4+ naïve/memory ratio (OR: 11.27, 95% CI 2.67–47.58, P = 0.001; OR: 8.50, 95% CI 1.90–38.14, P = 0.005) were independent predictors for tumor response to SBRT in the lung metastases of NSCLC patients. The tumor response of lung metastases a month after SBRT independently correlated with peripheral memory CD4+ T, memory CD8+ T, naïve CD4+ T, and CD4+ naïve/memory ratio. These findings could be helpful in incorporating additional treatments to improve clinical outcomes in the case of poor responders.