Implications of PD-L1 expression on the immune microenvironment in HER2-positive gastric cancer.
Mol Cancer
; 23(1): 169, 2024 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-39164705
ABSTRACT
In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS < 1 patients lacked notable benefits. We studied this in a real-world cohort of 106 HER2-positive, CPS < 1 patients and found no survival differences between those treated with anti-HER2 therapy alone or with added immunotherapy. Thus, we investigate the tumor microenvironment variations in 160 HER2-positive patients, CPS ≥ 1 cases exhibited elevated spatial effective scores of immune cells, including CD4, CD8 subtypes, and NK cells, compared to CPS < 1. Furthermore, through single-cell sequencing in eight HER2-positive individuals, gene expressions revealed regulation of T-cell co-stimulation in CPS ≥ 1 and IL-1 binding in CPS < 1 cases. Notably, we discovered a CPS < 1 subtype marked by CXCR4+M2 macrophages, associated with poor prognosis, whose proportion and expression were reduced when benefiting from anti-HER2 therapy. These findings suggest CPS ≥ 1 patients, due to their immune microenvironment composition, may respond better to anti-PD-1/PD-L1 therapy.
Full text:
1
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Receptor, ErbB-2
/
Tumor Microenvironment
/
B7-H1 Antigen
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Cancer
Journal subject:
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
China