Background: The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. Methods: This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan–Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. Results: Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08–0.57; P=0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56–25.36; P=0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. Conclusions: Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased post-conversion surgery recurrence.

Postoperative adjuvant chemotherapy (ACT) confers superior gastric cancer (GC) survival in the Eastern cohort. However, is the current standard of ACT already excessive, or is it still necessary to increase its intensity for specific subgroups? Tailored ACT strategies for GC depend on gradual exploration by clinical trials in selected patients. Thus, understanding the implications of previous and current research can help us respond wisely and design effective, rational trials, save medical resources and make better decisions in clinical practice. After reviewing and analyzing studies on ACT for GC patients undergoing curative resection, we found that research strategies for conducting “addition” ACT for specific stages of the disease have achieved great progress in making ACT more tailored and personalized in consideration of pathology stages. Furthermore, trials indicate that “addition” ACT strategies for GC patient subgroups based on histological characteristics might be helpful to move toward a more specific tailored and personalized management approach. Designing ACT research focused on different node statuses should also be conducted according to the biological specificity of lymph node (LN) metastasis. Therefore, future trials designed to determine tailored treatment based on histological and biological characteristics for specific subgroups are urgently needed and conducted as the theme of the 2019 American Society of Clinical Oncology (ASCO): Caring for Every Patient, Learning from Every Patient.

The prognosis of advanced gastric cancer (AGC) is extremely poor, and the therapeutic effect of traditional palliative chemotherapy is far from satisfactory. To overcome this bottleneck, palliative surgery resection, perioperative chemotherapy combined with surgical resection, hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), radiation therapy, molecular-targeted therapy have been explored in AGC. Although considerable progress has been achieved, there is still no overwhelming therapeutic method. Due to the high heterogeneity of AGC, it is particularly vital to reshaped the paradigm of gastric cancer therapy according to the characteristics of clinical classifications and molecular subtypes.

Background: Mismatch repair deficiency (dMMR) colorectal cancer (CRC) is characterized by abundant tumor-infiltrating lymphocytes and tertiary lymphoid structures (TLSs). However, while B cells are pivotal for TLS formation, their function and the signaling pathways driving their activation in dMMR CRCs remain undefined. Methods: Data from The Cancer Genome Atlas (TCGA) database analyzed by XCELL method and multiplex immunofluorescence (MIF) staining tissue slides were used to compare the abundance and distribution of TLSs and B cell populations between dMMR and proficient MMR cohorts. Then MLH1 knockdown models both in vitro and in vivo were used to mimic dMMR/high microsatellite instability (MSI-H) tumors and explore the influence of tumor cells on B cell behavior. Results: TCGA analysis and MIF staining revealed a significant association between memory B cell abundance, TLS formation, and improved prognosis in dMMR CRCs. In vivo MLH1 knockdown models showed that B cell depletion enhanced tumor growth and reduced the efficacy of anti-PD-1 treatment in dMMR CRCs. Furthermore, in vitro experiments demonstrated a dsDNA/STING/type I interferon (IFN)/STAT1/ ccl19 signaling pathway mediating the dMMR-induced increase in memory B cells. Conclusions: In conclusion, these findings show that CCL19 generated by STING/type I IFN/STAT1 pathway in dMMR/MSI-H CRC cells can promote the expansion of memory B cells, which suppresses tumor growth and enhances the efficacy of PD-1 blockade.