Targeting the Tumor Microenvironment with Interferon-β Bridges Innate and Adaptive Immune Responses (Cancer Cell, Volume 25, Issue 1, 37-48, 13 January 2014)

報告日期: 2014/05/30
報告時間: 3:10/4:00
報告學生: 李脩琦(以英文報告)
講評老師: 凌 斌
附件下載: 下載[1403-1396958484-1.pdf] 

Targeting the Tumor Microenvironment with Interferon-b Bridges Innate and Adaptive Immune Responses


Cancer Cell 25, 37–48, January 13, 2014

Speaker: Hsiu-Chi Lee

Commentator: Dr. Pin Ling

Date: May 30, 2014


Antibody (Ab) targeting oncogenic receptor has been applied in cancer therapy; however, the tumors intrinsic Ab resistance appears after prolonged treatment. In this paper, the authors propose that conjugation of IFNb with antioncogenic receptor Ab can target various carcinomas and overcome Ab resistance. This study shows that type I interferon is essential for Ab-mediated tumor regression. Treatment of mice bearing Ab-sensitive or Ab-resistant tumor with anti-EGFR-IFNb fusion protein revealed that IFNb enhances the anti-tumor effect of antibody. By using Rag1-/- mice, they found that adaptive immunity is required in the anti-EGFR-IFNb-mediated tumor regression. Furthermore, the IFNAR expression on host bone marrow-derived cells but not on tumor cells is necessary for the anti-tumor effect of Ab-IFNb. It suggests that the anti-EGFR-IFNb fusion protein may not directly kill the tumor cells but activate the host bone marrow-derived cells to alter the tumor microenvironment. Further study revealed that the anti-EGFR-IFNb fusion protein activate the IFNAR expressed dendritic cells to cross-prim the cytotoxic T lymphocytes inside tumor and draining lymph node. IN conclusion, this study establishes an Ab-based immunotherapy which bridges the innate and adaptive immune response in the tumor microenvironment and improves the cancer therapeutic effect of Ab.


Abbreviation: Ab, antibody; IFNb, interferon b; EGFR, epidermal growth factor receptor