Endogenous T Cell Responses to Antigens Expressed in Lung Adenocarcinomas Delay Malignant Tumor Progression

Michel DuPage et al. 2011. Cancer Cell. 19, 72-85 (2011)

Speaker: Jhih-Sin Lu (陸致信)                                      Time: 13:00~114:00,Mar.16, 2011

Commentator: Dr. Bei-Chang Yang (楊倍昌老師)      Place: Room 601

Abstract:

Tumor cell escaped from Immunosurveillance and downregulation of tumor antigen expression is a important character in tumorigenesis. Several mouse models provided many perspectives that tumor subverted immune response.¹² Although thesyngenic transplantation model is the most common model to study the interaction between tumor and immune system, those results are still in controversy due to large number of transplanted cells could result in strong inflammatory response.³ In this paper, the authors demonstrated that lung tumor expressed model antigen recruited large number of lymphocytes after tumor initiation, but the quantity of infiltrated lymphocytes decreased during tumor progression. Although the antigen-specific CD8 T cell responses are generated, the TNFα production are downregulated in CD8 T cell with exhaustion phenotype. To further confirm the dynamic CD8 T response to established tumor, the author transferred antigen-specific T cell to mouse, they found that the cytokine production of CD8 T cell is impaired in tumor-bearing mouse. The antigen expression and presentation on tumor is maintained in late stage of tumor development. Despite the suboptimal T cell response, the progression of immunogenic tumors is delayed. The author also found that loss of antigen and tumor elimination is induced in transplantation model and vaccination. The vaccination also enhanced CD8 T cell activation and promoted eradication of antigen-contained cancer cells. Taken together, this article provides a new insight about immune selection and manipulation of immune response against tumor.

References:

1. Douglas Hanahan et al. Hallmarker of cancer:The next generation Cell 144:646-674 (2011)

2. Dunn Gavin P. et al Interferons, immunity and cancer immunoediting Nat. Rev. Can. 6 836-848 (2005)

3.Khong, H,T. et al Natural selection of tumor variants in generation of “tumor escape “ phenotype Nat. Immunol. 3 999-1005 (2002)