Complement receptor C5aR1 blockade reprograms tumor-associated macrophages and synergizes with anti-PD-1 therapy in gastric cancer.

In gastric cancer (GC), the therapeutic response of immune checkpoint blockade (ICB) remains suboptimal. Targeting myeloid cell checkpoints might be feasible as adjuvant to current ICB regimens. We sought to evaluate the crucial role of C5aR1 TAMs in regulating antitumor immunity and the efficacy of combinatorial treatment with antiprogrammed cell death protein-1 (PD-1) and C5aR1 blockade.

Somatic ARID1A mutation stratifies patients with gastric cancer to PD-1 blockade and adjuvant chemotherapy.

Background: AT-rich interaction domain 1A (ARID1A) encodes a vital component of switch/sucrose non-fermentable chromatin-remodeling complex. Given its association with genomic instability, we conducted this study to determine whether ARID1A mutation status had an impact on therapeutic responsiveness in gastric cancer (GC), especially combinatory chemo-immunotherapy.

Methods: We retrospectively enrolled a total of 1162 patients from five independent cohorts.

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.

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.