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Updated: Jun 5, 2026
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression
Michel DuPage1, Ann F Cheung, Claire Mazumdar
1Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Abstract:
Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here, we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors.
Insights
Tumor neoantigens can engage the immune system, but T-cell responses to lung cancers are not sustained. Therapeutic strategies like vaccination can overcome immune escape by targeting these neoantigens.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Somatic mutations in tumors generate neoantigens, which are crucial for adaptive immune responses against cancer.
- Understanding the dynamics of the immune response to tumor neoantigens is vital for developing effective cancer immunotherapies.
Purpose of the Study:
- To investigate the host immune response to experimentally introduced tumor neoantigens in a mouse model of lung cancer.
- To explore the mechanisms of immune evasion and potential therapeutic strategies against neoantigen-expressing tumors.
Main Methods:
- Genetically engineered mouse model of lung cancer with introduced exogenous antigens mimicking tumor neoantigens.
- Monitoring of endogenous T-cell responses, tumor infiltration, and malignant progression.
- Evaluation of therapeutic interventions including tumor cell line transplantation and prophylactic vaccination.
Main Results:
- Endogenous T-cells infiltrated tumors and initially delayed cancer progression.
- T-cell infiltration waned over time, leading to tumor immune escape despite persistent antigen expression.
- Tumor eradication or selection of antigen-loss variants occurred following transplantation or vaccination.
Conclusions:
- The immune response to tumor neoantigens is dynamic and subject to immune evasion mechanisms.
- Targeting neoantigens via vaccination or other immunotherapies holds promise but must account for dynamic immune escape.
- This study provides insights into the complex interplay between tumors and the immune system in cancer progression.
