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Purpose: To investigate the impact of delayed adjuvant imatinib on GIST patients with high risk of recurrence. Method: Adult GIST patients were retrospectively collected from our hospital between 2011 and 2018, and patients having high risk of recurrence were included for subsequent analyses. The primary endpoint was recurrence-free survival (RFS). Results: According to the interval between the radical surgery and the beginning of adjuvant imatinib, 222 patients were divided into three groups: group A (≤ 2 months, n = 41), group B (2–≤ 4 months, n = 113), and group C (4–≤ 6 months, n = 68). Univariate, multivariate, and survival analyses all showed that patients in group A had significantly more favorable RFS than those in group C but not group B, and patients taking adjuvant imatinib for over 12 months were also associated with longer RFS comparing to adjuvant imatinib of ≤ 12 months. When stratified by the duration of adjuvant imatinib, no significant differences were found in RFS among groups A, B, and C for adjuvant imatinib of ≤ 12 months. While for adjuvant imatinib of over 12 months, both groups A and B had significantly more favorable RFS than group C, and no significant difference in RFS was found between group A and B. Conclusion: Delayed postoperative adjuvant imatinib for over 4 months in patients with high risk of recurrence of GIST may lead to worse RFS, and longer treatment with shorter delay has best results. [ABSTRACT FROM AUTHOR]

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163- macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163- macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163- macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes. [ABSTRACT FROM AUTHOR]