[Clinical significance of combined therapy with immune checkpoint inhibitor in perioperative treatment for locally advanced gastric cancer or adenocarcinoma of gastroesophageal junction].

ABSTRACT

The clinical application of immune checkpoint inhibitor (ICI) offers novel treatment modality for locally advanced gastric cancer (LAGC) and adenocarcinoma of the gastroesophageal junction (AGEJ), with the crucial benefit of providing higher cure rates. These agents have become part of standard treatments in the perioperative setting for selected cases, such as tumor with MSI-H/dMMR, high expression of CPS (≥5) or EBV (+), MSI-H and MSS/TP53+ according to tumor immunohistochemical, genetic testing or molecular characterization. An in-depth understanding of the immune response mechanisms in "cold" and "hot" tumors enables us to better identify ICI beneficiary and further provide a rationale for converting nonresponsive "cold" tumors into responsive "hot" tumors, subsequently allowing nonresponders to benefit from ICI immunotherapy. Several recent clinical trials clearly demonstrated a synergistic and complementary effect of combining ICI with chemotherapy or chemoradiotherapy, as well as combining ICI with anti-HER2 or anti-VEGF/VEGFR and chemotherapy. Compared with chemotherapy alone, the combination treatment can significantly improve pCR, MRR or ypT0N0, and is expected to improve the prognosis. This article reviews the results of a series of clinical trials in recent years in the field of perioperative application of ICI with other modalities in LAGC/AGEJ, aiming at expanding upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC/AGEJ and exploring the feasibility of new perioperative combined immunotherapy in the future.