Impact of clonal TP53 mutations with loss of heterozygosity on adjuvant chemotherapy and immunotherapy in gastric cancer.

Background: This study aimed to reveal the effect of TP53 status on clinical outcomes and underlying mechanism in gastric cancer (GC) patients.

Methods: TP53 status was divided into three groups according to genome sequencing, namely clonal mutations with LOH (C-LOH), clonal diploid or subclonal mutations (CD-SC), and wild type (WT). The p53 protein activity was divided into over-expression (OE), Null and WT according to immunohistochemical staining.

Clinical outcome and molecular landscape of patients with ARID1A-loss gastric cancer.

Chromatin remodelers are commonly altered in human cancer. The mutation of AT-rich interactive domain 1A (ARID1A) in gastric cancer (GC), a component of the SWI/SNF chromatin remodeling complex, was proven associated with treatment response in our previous study. However, ARID1A loss of function was caused not only by mutations but also copy number deletions.

Targeting myeloid checkpoint Siglec-10 reactivates antitumor immunity and improves anti-programmed cell death 1 efficacy in gastric cancer.

Objective: Immunotherapy has not yielded satisfactory therapeutic responses in gastric cancer (GC). However, targeting myeloid checkpoints holds promise for expanding the potential of immunotherapy. This study aims to evaluate the critical role of Siglec-10 tumor-associated macrophages (TAMs) in regulating antitumor immunity and to explore the potential of the myeloid checkpoint Siglec-10 as an interventional target.

Intratumoral PD-1CD8 T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

Background: Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1CD8 T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1CD8 T cells in the tumour microenvironment and its clinical significance in GC.

Designs: This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group.

Impact of intratumoural CD96 expression on clinical outcome and therapeutic benefit in gastric cancer.

CD96 was identified as a novel immune checkpoint. However, the role of CD96 in the gastric cancer (GC) microenvironment remains fragmentary. This study aimed to probe the clinical significance of CD96 to predict prognosis and therapeutic responsiveness, and to reveal the immune contexture and genomic features correlated to CD96 in GC patients.

Intratumoral IL-1R1 expression delineates a distinctive molecular subset with therapeutic resistance in patients with gastric cancer.

Background: With the essential role of interleukin-1 signaling in cancer-related inflammation, IL-1R1, the main receptor for both IL-1α and IL-1β, demonstrated therapeutic potential in several types of cancer, which has been put into clinical trials. However, the expression profile and critical role of IL-1R1 in gastric cancer (GC) remain obscure. This study aimed to investigate the prognostic significance of IL-1R1 expression and its predictive value for chemotherapy and immunotherapy in GC.

TIM3 cells in gastric cancer: clinical correlates and association with immune context.

Background: T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a crucial immune checkpoint and is considered as an emerging target for cancer treatment. However, the clinical significance and immune-related role of TIM3 cells in gastric cancer remain unknown. This study aimed to investigate the clinical significance of tumour-infiltrating TIM3 cells and their association with immune contexture in gastric cancer.

Impact of intratumoural CD73 expression on prognosis and therapeutic response in patients with gastric cancer.

Aim: CD73 overexpression has been reported in several malignancies and is considered to be a novel immune checkpoint. However, the role and significance of CD73 in gastric cancer (GC) still remain obscure. We aim to investigate the role of CD73 expression in predicting prognosis, shaping immune contexture and guiding therapeutic strategy in GC.

Intratumoral CXCR5CD8T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer.

Studies that examined an association between CD8T and prognosis in gastric cancer are inconsistent, and a distinct population of CXCR5CD8T associated with better overall survival has been reported among various malignancies. Here, we show that the abundance of intratumoral CXCR5CD8T cells is associated with better overall survival in patients with gastric cancer. Patients with TNM II + III gastric cancer with higher intratumoral CXCR5CD8T cell infiltration are more likely to benefit from adjuvant chemotherapy.

Poor clinical outcomes and immunoevasive contexture in CXCL13+CD8+ T cells enriched gastric cancer patients.

As an adverse survival prognosticator, chemokine (C-X-C motif) ligand 13 (CXCL13) has been studied in several types of malignancies. The secretion and physiological roles of CXCL13 in follicular helper T cells (T) cells have been well described, while the clinical significance of CD8 tumor-infiltrating lymphocytes (TILs)-associated CXCL13 remains unknown. This study aims to investigate the clinical significance of CXCL13CD8 T cells in survival and chemotherapeutic responsiveness prediction in gastric cancer.

Intratumoral Foxp3RORγt T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.

Background: Foxp3RORγt T cells possess both characteristics of regulatory T cells and T helper 17 cells and show significant immunoregulatory functions in autoimmune diseases. However, the role and clinical significance of Foxp3RORγt T cells in gastric cancer remains unclear.

Methods: We enrolled 452 gastric cancer tissue microarray samples and 60 fresh tumor tissue samples from Zhongshan Hospital.

Clinical Outcomes and Immune Metrics in Intratumoral Basophil-Enriched Gastric Cancer Patients.

Background: Accumulation of basophils has been reported in several malignancies. In gastric cancer, the relation between tumor-infiltrating basophils and patient overall survival and chemotherapeutic responsiveness still remains obscure.

Objective: We aimed to investigate the postoperative prognostic and predictive significance of basophils to survival outcomes and chemotherapeutic responsiveness in resectable gastric cancer.

CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration.

Background: CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear.

Methods: Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed.

Tumor-infiltrating podoplanin cells in gastric cancer: clinical outcomes and association with immune contexture.

Podoplanin (PDPN) has been proved to have significant immunoregulatory effects in several types of malignancies and is considered to be a novel immune checkpoint molecule. However, the clinical significance of PDPN and its potential influence on immune contexture in gastric cancer remain obscure. Here, we aimed to investigate the clinical outcomes and immunoregulatory role of tumor-infiltrating PDPN cells (tPDPNs) in gastric cancer.

Lymphocyte-activation gene 3 expression associates with poor prognosis and immunoevasive contexture in Epstein-Barr virus-positive and MLH1-defective gastric cancer patients.

Lymphocyte activation gene 3 (LAG-3) is a transmembrane immune checkpoint that facilitates immune escape via suppressing T-cell-mediated anti-tumor immunity. The role of LAG-3 in gastric cancer is little known. Consequently, we assessed the clinical significance of LAG-3 in gastric cancer.

Poor Clinical Outcomes and Immunoevasive Contexture in Intratumoral IL-10-Producing Macrophages Enriched Gastric Cancer Patients.

Objective: To investigate the clinical significance of IL-10+ tumor-associated macrophages (TAMs) in gastric cancer.

Background: Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10+ TAMs in gastric cancer remains obscure.