Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. Significance: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985

The outbreak of COVID‐19 coronavirus disease around the end of 2019 has become a pandemic. The preferred method for COVID‐19 detection is the real‐time polymerase chain reaction (RT‐PCR)‐based technique; however, it also has certain limitations, such as sample‐dependent procedures with a relatively high false negative ratio. We propose a safe and efficient method for screening COVID‐19 based on Raman spectroscopy. A total of 177 serum samples are collected from 63 confirmed COVID‐19 patients, 59 suspected cases, and 55 healthy individuals as a control group. Raman spectroscopy is adopted to analyze these samples, and a machine learning support‐vector machine (SVM) method is applied to the spectrum dataset to build a diagnostic algorithm. Furthermore, 20 independent individuals, including 5 asymptomatic COVID‐19 patients and 5 symptomatic COVID‐19 patients, 5 suspected patients, and 5 healthy patients, were sampled for external validation. In these three groups—confirmed COVID‐19, suspected, and healthy individuals—the distribution of statistically significant points of difference showed highly consistency for intergroups after repeated sampling processes. The classification accuracy between the COVID‐19 cases and the suspected cases is 0.87 (95% confidence interval [CI]: 0.85–0.88), and the accuracy between the COVID‐19 and the healthy controls is 0.90 (95% CI: 0.89–0.91), while the accuracy between the suspected cases and the healthy control group is 0.68 (95% CI: 0.67–0.73). For the independent test dataset, we apply the obtained SVM model to the classification of the independent test dataset to have all the results correctly classified. Our model showed that the serum‐level classification results were all correct for independent test dataset. Our results suggest that Raman spectroscopy could be a safe and efficient technique for COVID‐19 screening.

In this study, we sought to investigate the potential application of γδ T cell-derived extracellular vesicles (γδTDEs) as drug delivery system (DDS) for miR-138 in the treatment of oral squamous cell carcinoma (OSCC). Our data showed that overexpression of miR-138 in γδ T cells obtained miR-138-rich γδTDEs accompanying increased expansion and cytotoxicity of γδ T cells. γδTDEs inherited the cytotoxic profile of γδ T cells and could efficiently deliver miR-138 to OSCC cells, resulting in synergetic inhibition on OSCC both in vitro and in vivo. The pre-immunization by miR-138-rich γδTDEs inhibited the growth of OSCC tumors in immunocompetent C3H mice, but not in nude mice, suggesting an immunomodulatory role by miR-13-rich γδTDEs. γδTDEs and miR-138 additively increased the proliferation, interferon-γ (IFN-γ) production, and cytotoxicity of CD8+ T cells against OSCC cells. Only delivered by γδTDEs can miR-138 efficiently target programmed cell death 1 (PD-1) and CTLA-4 in CD8+ T cells. We conclude that γδTDEs delivering miR-138 could achieve synergetic therapeutic effects on OSCC, which is benefited from the individual direct anti-tumoral effects on OSCC and immunostimulatory effects on T cells by both γδTDEs and miR-138; γδTDEs could serve as an efficient DDS for microRNAs (miRNAs) in the treatment of cancer.

Background: To retrospectively analyze whether primary tumor volume and primary nodal volume could be considered independent prognostic factors for nasopharyngeal carcinoma treated with intensity-modulated radiation therapy. Methods: Three hundred sixty-three consecutive nasopharyngeal carcinoma (NPC) patients who were stage I-IVa+b and treated with intensity-modulated radiotherapy (IMRT) in our center from October 2003 to October 2005 were analyzed retrospectively. The predictive ability of gender, age, T and N stage, combined chemotherapy, primary tumor and nodal volume for the 5-year local control (LC), distant-metastasis free survival (DMFS) and overall survival (OS) rate were investigated. Primary tumor and nodal volume were measured based on registration of magnetic resonance imaging (MRI) with contrast-enhanced computed tomography (CT) images. The Kaplan–Meier method was used for survival analysis, the log-rank test was used for univariate analyses and the Cox proportional hazard model was used for multivariate prognostic analyses. Results: The mean value of primary tumor and nodal volume were 31.5 ml and 9.7 ml. The primary tumor and nodal volume were respectively divided into four groups for analysis (primary tumor volume: TV1≤20 ml, 20<TV2≤30 ml, 3040 ml; primay nodal volume: NV1≤5 ml, 5<NV2≤10 ml, 1020 ml). In univariate analysis, the 5-year LC and DMFS rate for TV4 was significantly decreased compared to the other groups (LC: p40 ml was an adverse prognostic factor for the 5-year local regional control (LRC) rate (RR 2.454, p=0.002). Primary nodal volume had no statistical significance in predicting 5-year LRC, DMFS and OS rate in multivariate analysis. Conclusions: Primary tumor volume could predict LRC rate of NPC patients, and the primary tumor volume of 40 ml may be the cut-off. Primary nodal volume may have predictive significance, but more data are needed. These factors should be considered in the TNM staging system of NPC for better estimates of prognosis.