Multiple immunofluorescence stains revealed significantly fewer CD3 + , CD8 + , CD56 + , and CD68 + immune cells in the tumor parenchyma and stroma in HER2-positive AFPGC patients than in HER2-negative and AFP-normal gastric cancer patients.<h4>Conclusions</h4>Compared with current treatments, parts of HER2-positive AFPGC can achieve equivalent ORR and survival benefits, especially with HER2-targeted, anti-PD-1 antibody and chemotherapy. Here, ERBB2 is linked to gastric cancer.