PD-L1 and HER2 expression in gastric adenocarcinoma and their prognostic significance

Abstract

Background: The upregulation of programmed death-ligand 1 (PD-L1) and epidermal growth factor receptor 2 (HER2) may play a role in gastric adenocarcinoma (GAC). Aim: To study PD-L1 and HER-2 expression and prognosis in GAC. Methods: PD-L1 and HER2 expression was determined in tumor tissues of 75 patients with GAC. The correlations between PD-L1, HER2 expression, and clinicopathological factors were analyzed. Results: The positive expression rate for PD-L1 was 57.3% (43/75) and the HER2 over-expression rate was 17.3% (13/75). PD-L1 expression negatively correlated with the grade of GAC differentiation (r = -0.26, P < 0.05). Approximately 85% of HER2-positive GACs were found to be PD-L1-positive and PD-L1 expression positively correlated with HER2 overexpression. The TNM stage and combined HER2 and PD-L1 expression were independent prognostic factors affecting the survival of patients with GAC. The median overall survival and recurrence-free survival of groups I (HER2 overexpression and PD-L1 positive), II (HER2 overexpression and PD-L1 negative), III (No HER2 overexpression and PD-L1 positive) and IV (No HER2 overexpression and PD-L1 negative) were (47 (17-77), 15 (0-44), 81 (62-101), and 78 (60-98) months, respectively. Conclusion: PD-L1 expression is upregulated in more than half of patients with GAC. Anti-PD-L1 treatment combined with anti-HER2 therapy may benefit patients with locally advanced GAC with HER2 overexpression.

Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma

“…A significant prognostic value of ERBB2 CN, TMB and genomic alterations associated with HER2 signaling could not be confirmed in this cohort. PD-L1 expression has been found to co-occur with HER2-positivity in 25-85% of GC/GEJ patients [21][22][23]32]. With 47.3% of HER2+/PD-L1+ patients, our result falls within the reported range.…”

“…Recent studies like the KEYNOTE-811 explored the efficacy of anti-PD-L1 treatment in HER2-positive mGC/mGEJC showing that the combination of pembrolizumab and trastuzumab with chemotherapy leads to improved response rates compared to treatment with chemotherapy and trastuzumab alone [21]. In addition, the combined expression of PD-L1 and HER2 was found to be a positive prognostic factor for survival in GC [22]. Findings from a preliminary biomarker analysis of the DESTINY-Gastric03 trial, showed a large overlap between HER2 and PD-L1 expression in 85% of the patients GC or GEJC [23].…”

Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications

“…HER2 overexpression correlates with PD-L1 overexpression [ 138 ]. One study found that HER2 knockdown in PD-L1/HER2+ GC organoids resulted in a decrease in PD-L1 expression [ 139 ].…”

“…Furthermore, in co-cultures with immune cells, cytotoxic lymphocytes proliferated more and caused an increase in tumour cell death [ 139 ]. Another study reported that 85% of HER2-positive gastric adenocarcinoma (GACs) were characterized by a positive PD-L1 expression and PD-L1 expression positively correlated with HER2 overexpression [ 138 ]. These data showed that the combination of anti-PD-L1 treatment with anti-HER2 therapy may have a positive effect in AGC patients with HER2 overexpression [ 138 ].…”

“…Another study reported that 85% of HER2-positive gastric adenocarcinoma (GACs) were characterized by a positive PD-L1 expression and PD-L1 expression positively correlated with HER2 overexpression [ 138 ]. These data showed that the combination of anti-PD-L1 treatment with anti-HER2 therapy may have a positive effect in AGC patients with HER2 overexpression [ 138 ]. Clinical trials investigating the addition of checkpoint inhibitors to anti-HER2 targeted treatments are ongoing and will be analysed in depth in the following section.…”