Immune Responses to Epidermal Growth Factor Receptor (EGFR) and Their Application for Cancer Treatment

Abstract

Epidermal growth factor receptor (EGFR) is a prototypic cell-surface receptor belonging to the ErbB/HER onocogene family. Overexpression or somatic mutations of EGFR have been reported to play an important role in tumorigenesis in various types of epithelial cancers. Therefore, targeting of EGFR with specific blocking antibodies or inhibitors have been developing for treatment for EGFR-associated tumors. Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied, but only limited information on the immune responses to EGFR in cancer has been currently available. In this review, we have summarized the available data and discussed potential clinical importance of the anti-EGFR immune responses and EGFR-mediated immune regulation in cancer. Several lines of evidence suggest that cellular and humoral immune responses to EGFR might be useful as a marker and/or target for cancer therapy against EGFR-associated tumors. In addition, recent studies suggest the critical roles of EGFR-mediated signaling in regulation of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1) in tumor cells. Further studies are warranted to clarify the impact of the anti-EGFR immune responses and EGFR-mediated immunomodulation for clinical application for cancer treatment.

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non‐small cell lung cancer

“…Although there is no evidence of CD47 regulation by EGFR, different reports in vitro show that PD‐L1 can be either upregulated or downregulated depending on the activation or inhibition of EGFR‐mutant cell lines . Consistently, blocking the PD1/PDL‐1 axis in EGFR‐mutant lung tumors of mice results in better OS . This association of EGFR activating mutations, mainly exon 19 deletions and L858R with high PD‐L1 expression, has also been observed in patients with lung adenocarcinoma histology; however, subpopulations with this characteristic are less .…”

EGFR‐targeted therapy alters the tumor microenvironment in EGFR‐driven lung tumors: Implications for combination therapies

“…Many factors operating within the TME inhibit the therapeutic effects of an immune checkpoint blockade . Notably, the oncogene EGFR has been shown to influence the host immune response in many ways . Here, we investigated the dynamic changes occurring in the immune microenvironment after EGFR inhibition and demonstrated a sustained increase in CD3 + lymphocytes following the treatment with sensitive TKIs.…”

“…33 Notably, the oncogene EGFR has been shown to influence the host immune response in many ways. [34][35][36] Here, we investigated the dynamic changes occurring in the immune microenvironment after EGFR inhibition and demonstrated a sustained increase in CD3 + lymphocytes following the treatment with sensitive TKIs. Further analysis of lymphocyte subsets identified a short-term increase in CD8 + cells, while this elevation in the proportion of CD8 + cells was not observed with continued EGFR inhibition.…”

Chimeric antigen receptor T cells: a novel therapy for solid tumors

“…EGFR is expressed in the skin, gastrointestinal system, kidney, and other normal tissues at the physiological level; however, it is aberrantly activated in many epithelial tumors, such as lung cancer, pancreatic cancer, colorectal cancer, breast cancer, and head and neck squamous cell carcinoma (HNSCC) [32, 33]. EGFR plays central roles in regulation of cellular multiplication, differentiation, and metastasis, and the overexpression of EGFR is related to a more aggressive clinical progression and poor prognosis [34, 35].…”