Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer

Abstract

The programmed death receptor 1/programmed death receptor ligand 1 axis (PD-1/PD-L1) is involved in tumor immune escape and is a potential prognostic biomarker and anti-tumor immunotherapy target in patients with gastric cancer (GC). However, the results of studies obtained in recent years have been inconsistent. The present study aimed to determine the possible predictive significance of PD-L1 in conjunction with three proteins linked with PD-L1 regulation in patients with primary GC. In the present study, the PD-L1, human epidermal growth factor receptor 2 (HER2), cluster of differentiation (CD)133 and microphage-associated CD68 expression levels were identified by multiplexed immunohistochemistry and assessed by automated pathological analysis system in 93 GC tumors and neighboring normal tissues arrayed on the same tissue microarray. All four proteins were statistically analyzed in relation to the clinicopathological characteristics. The expression levels of HER2, CD133 and CD68 were considerably higher in cancer tissues compared with neighboring normal tissues (P<0.05), however, the reverse trend was detected for PD-L1 expression (P=0.0577), particularly in tumor nest (TN; P<0.05). There was no significant correlation between the HER2 and CD133 expression levels and clinicopathological factors. However, significant relationships were found between PD-L1 expression and the TNM stage, pathological differentiation and survival status of patients (P<0.05). Moreover, survival time was prolonged in individuals with elevated PD-L1 expression in TN and GC tissues, but no significant correlation was identified (P=0.0881). The CD68 expression level in tumor stroma, but not in TN, was significantly correlated with poor pathological differentiation in patients with GC (P<0.05). However, PD-L1+CD68+ macrophages were strongly related to lower tumor size (diameter <5 cm), early TNM stage (stage I+II), good pathological differentiation and overall survival in TN (P<0.05). In conclusion, PD-L1+CD68+ macrophage infiltration in TN might be a potential indicator of prognosis in patients with primary GC and merits further investigation.

Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update

“…In the TN ( p < 0.05), PD-L1+CD68+ macrophages were significantly associated with reduced tumor mass (<5 cm), early TNM stage (stages I+II), excellent OS, and pathological differentiation. They may also be a viable prognostic indicator in primary GC patients [ 11 ]. The number of neutrophils, macrophages, CD8+ T cells, and dendritic cells was positively associated with the degree of integrin subunit beta 1 (ITGB1) expression.…”

“…disulfidptosis-related gene prognostic risk model [4] -M2 macrophages were strongly correlated with a high PANscore [5] predictive signature AC129926.1, AC023511.1, AP002954.1, LINC01537, and TMEM7 based on CRLs [6] -ARLSig has strong predictive value for the survival of GC patients [7] -PRS was created using the TCGA, GSE15459, GSE26253, GSE62254, and GSE84437 datasets [8] -PI3K pathway linked to PD-L1 positivity is linked to increased immunotherapy efficacy [9] potentially valid serum predictive markers for identifying individuals who might profit from PD-1 inhibitors paired with chemotherapy include IL-6, IL-2, IL-17A, and NLR [10] -PD-L1+CD68+ macrophages may be a viable prognostic indicator in primary GC patients [11] -ITGB1 may be an effective prognostic biomarker and a useful predictor of outcome for GC patients receiving anti-PD-1 medication [12] a reduced tumor mass, absence or small number of lymph node metastases, and a large combined positive score; neoadjuvant chemotherapy plus PD-1 antibodies for the prediction of pCR in AGC patients undergoing neoadjuvant chemotherapy combined with PD-1 antibody immunotherapy [13] memory PD-1+CD8+ T cells and the ratio of PD-1+CD8+ T cells to PD-1+CD4+ T cells may be useful for identifying individuals who would benefit from immunotherapy among AGC patients [14] the CD4+/CD8+ ratio may be a potential predictive indicator for patients under PD-1 inhibitor-based combination therapy for advanced gastric and esophageal cancer, and it can independently predict dermatological damage [15] -MFSD2A may function as a prognostic biomarker for the response to anti-PD-1 immunotherapy in AGC patients [16] the peripheral CD4+ T-cell subset has shown significant predictive value for therapeutic response and longer survival in AGC patients [17] patients with GC receiving combination immunotherapy are predicted to respond better when HSPA4 is upregulated [18] the combination of Tregs, Ki-67, and age (65 years or older) can more accurately predict the likelihood of unfavorable responses [19] the incidence of irAEs could serve as a stand-in marker for ICIs [20] utilizing biomarkers based on the numbers of various lymphocyte subpopulations, it is possible to predict the clinical prognosis and efficacy of immunotherapy in patients with AGC [21] a negative correlation between CRABP2 and the immune checkpoint markers PD-1, PD-L1, and CTLA-4 was observed [22] Table 2. Major developments in genetic predictive factors research.…”