Human cancer evolution in the context of a human immune system in mice

Autor: Odd L. Gammelgaard, Mikkel G. Terp, Birgitte Preiss, Henrik J. Ditzel
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Molecular Oncology, Vol 12, Iss 10, Pp 1797-1810 (2018)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12374
Popis: Immunotherapy is one of the most promising cancer treatment modalities, but the lack of appropriate preclinical in vivo models hampers the development of novel immunotherapeutic strategies. Here, we studied the ability of transplanted human cancer cells to form primary tumors and metastasize in humanized immune system (HIS) mice created by transfer of CD34+ human hematopoietic stem cells. All tested transplanted cancer cell lines developed primary tumors that progressed nearly synchronously. Spontaneous lung and liver metastases developed from both orthotopic and ectopic transplanted cancer cells, and the ability to spread inversely correlated with the extent of CD8+ infiltration in the primary tumor. Further analysis revealed that interactions between the cancer model and the tumor‐infiltrating lymphocytes created tumor microenvironments (TMEs) resembling clinical cancers. Some models were largely immune cell‐excluding, while others appeared to develop adaptive resistance to immune‐mediated destruction by increased expression of programmed death ligand 1 (PDL1) and recruitment of human regulatory T cells. Our data suggest that HIS mice may provide a promising in vivo tumor model for evaluating immune modulatory anticancer therapies. Moreover, our study identified different tumor models resembling specific types of human TMEs, rendering each beneficial for addressing disease‐specific issues.
Databáze: Directory of Open Access Journals
Externí odkaz: