Significance
The benefit of 5-FU/platinum with anti-PD-1 in first-line advanced gastric cancer is limited to patient subgroups. Using a trial with sequential anti-PD-1, we show coordinated induction of multicellular TME hubs informs the ability of anti-PD-1 to potentiate T cell-driven responses. Differential TME hub development highlights features that underlie clinical outcomes. This article is featured in Selected Articles from This Issue, p. 695.