Related Experiment Video

Updated: Jan 14, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.5K

Synergistic camrelizumab therapy inhibits P53-mutant osimertinib-resistant solid lung adenocarcinoma via the TGF-β

Xiaoqin Shi1, Min Zheng2, Xiaolan Wang1

  • 1Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Translational Lung Cancer Research
|October 24, 2025
PubMed
Abstract

Insights

Immune checkpoint inhibitors (ICIs) show promise for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistant lung adenocarcinomas (LACs). Targeting the transforming growth factor-beta (TGF-β) pathway enhances treatment efficacy in these resistant LACs.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Lung adenocarcinomas (LACs) exhibit varied responses to immune checkpoint inhibitors (ICIs) after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance.
  • Understanding the tumor microenvironment (TME) and programmed cell death ligand 1 (PD-L1) regulation is crucial for optimizing ICI therapy in EGFR-mutant LACs.
  • The role of the transforming growth factor-beta (TGF-β) signaling pathway in TME remodeling and treatment resistance requires investigation.

Purpose of the Study:

  • To explore the regulatory mechanisms of EGFR-mutant LAC and PD-L1 expression within the TME.
  • To investigate the pathological responses and underlying mechanisms in osimertinib-resistant patients treated with ICIs.
  • To elucidate the impact of the TGF-β signaling pathway on TME and treatment outcomes.

Main Methods:

  • Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets.
  • PD-L1 and cytokine expression were assessed using immunohistochemistry and cytometric bead array.
  • Osimertinib-resistant LAC xenografts in immune-humanized mice were used to evaluate pathological responses to EGFR-TKI and ICI, with TGF-β signaling proteins, pERK1/2, pSTAT3, and PD-L1 analyzed via western blotting. Clinical responses in 12 patients were also observed.

Main Results:

  • GO and KEGG analyses identified "cytokine-cytokine receptor interaction" and "TGF-beta signaling pathway" as key pathways.
  • PD-L1 expression was found to be heterogeneously regulated by synergistic IL-6/STAT3, TGF-β, and EGFR pathways.
  • EGFR-TKI plus ICI treatment led to significant tumor remission and TGF-β signaling pathway inhibition in mouse models, with observed clinical benefits in osimertinib-resistant LACs treated by ICI.

Conclusions:

  • The TGF-β signaling pathway is implicated in PD-L1 expression and pathological remission following EGFR-TKI and ICI treatment.
  • Solid osimertinib-resistant LACs may benefit from ICI therapy through the inhibition of the TGF-β signaling pathway.
Keywords:
Lung adenocarcinoma (LAC)immune checkpoint inhibitor (ICI)osimertinib-resistancetransforming growth factor-β (TGF-β)

More Related Videos

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.5K
Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation15:04

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

Published on: January 19, 2019

12.7K

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K