論文 - 詳細
| RRC ID | 69462 |
|---|---|
| 著者 | Sato Y, Fu Y, Liu H, Lee MY, Shaw MH. |
| タイトル | Tumor-immune profiling of CT-26 and Colon 26 syngeneic mouse models reveals mechanism of anti-PD-1 response. |
| ジャーナル | BMC Cancer |
| Abstract |
BACKGROUND:Immune checkpoint blockade (ICB) therapies have changed the paradigm of cancer therapies. However, anti-tumor response of the ICB is insufficient for many patients and limited to specific tumor types. Despite many preclinical and clinical studies to understand the mechanism of anti-tumor efficacy of ICB, the mechanism is not completely understood. Harnessing preclinical tumor models is one way to understand the mechanism of treatment response. METHODS:In order to delineate the mechanisms of anti-tumor activity of ICB in preclinical syngeneic tumor models, we selected two syngeneic murine colorectal cancer models based on in vivo screening for sensitivity with anti-PD-1 therapy. We performed tumor-immune profiling of the two models to identify the potential mechanism for anti-PD-1 response. RESULTS:We performed in vivo screening for anti-PD-1 therapy across 23 syngeneic tumor models and found that CT-26 and Colon 26, which are murine colorectal carcinoma derived from BALB/c mice, showed different sensitivity to anti-PD-1. CT-26 tumor mice were more sensitive to the anti-PD-1 antibody than Colon 26, while both models show similarly sensitivity to anti-CTLA4 antibody. Immune-profiling showed that CT-26 tumor tissue was infiltrated with more immune cells than Colon 26. Genomic/transcriptomic analyses highlighted thatWnt pathway was one of the potential differences between CT-26 and Colon 26, showing Wnt activity was higher in Colon 26 than CT-26. . CONCLUSIONS:CT-26 and Colon 26 syngeneic tumor models showed different sensitivity to anti-PD-1 therapy, although both tumor cells are murine colorectal carcinoma cell lines from BALB/c strain. By characterizing the mouse cells lines and tumor-immune context in the tumor tissues with comprehensive analysis approaches, we found that CT-26 showed "hot tumor" profile with more infiltrated immune cells than Colon 26. Further pathway analyses enable us to propose a hypothesis that Wnt pathway could be one of the major factors to differentiate CT-26 from Colon 26 model and link to anti-PD-1 response. Our approach to focus on preclinical tumor models with similar genetic background but different sensitivity to anti-PD-1 therapy would contribute to illustrating the potential mechanism of anti-PD-1 response and to generating a novel concept to synergize current anti-PD-1 therapies for cancer patients. |
| 巻・号 | 21(1) |
| ページ | 1222 |
| 公開日 | 2021-11-13 |
| DOI | 10.1186/s12885-021-08974-3 |
| PII | 10.1186/s12885-021-08974-3 |
| PMID | 34774008 |
| PMC | PMC8590766 |
| MeSH | Animals Base Sequence Cell Line, Tumor Colonic Neoplasms / drug therapy* Colonic Neoplasms / genetics Colonic Neoplasms / immunology Disease Models, Animal* Exome Sequencing Female Gene Expression Profiling Immune Checkpoint Inhibitors / immunology Immune Checkpoint Inhibitors / pharmacology* Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Neoplasm Transplantation Transcriptome Wnt Signaling Pathway* |
| IF | 3.15 |
| リソース情報 | |
| ヒト・動物細胞 | Colon-26(RCB2657) |