A Spontaneous Melanoma Mouse Model Applicable for a Longitudinal Chemotherapy and Immunotherapy Study

Kevinn Eddy, Kajal Gupta, Jeffrey C. Pelletier, Allison L. Isola, Christina Marinaro, Maryam Abdur Rasheed, Joseph Campagnolo, Mohamad Naser Eddin, Marco Rossi, Anna Fateeva, Kenneth Reuhl, Raj Shah, Ann K. Robinson, Anna Chaly, Katie B. Freeman, Wenjin Chen, Jesus Diaz, Philip Furmanski, Ann W. Silk, Allen B. ReitzAndrew Zloza, Suzie Chen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Mouse models that reflect human disorders provide invaluable tools for the translation of basic science discoveries to clinical therapies. However, many of these in vivo therapeutic studies are short term and do not accurately mimic patient conditions. In this study, we used a fully immunocompetent, transgenic mouse model, TGS, in which the spontaneous development of metastatic melanoma is driven by the ectopic expression of a normal neuronal receptor, mGluR1, as a model to assess longitudinal treatment response (up to 8 months) with an inhibitor of glutamatergic signaling, troriluzole, which is a prodrug of riluzole, plus an antibody against PD-1, an immune checkpoint inhibitor. Our results reveal a sex-biased treatment response that led to improved survival in troriluzole and/or anti−PD-1−treated male mice that correlated with differential CD8+ T cells and CD11b+ myeloid cell populations in the tumor−stromal interface, supporting the notion that this model is a responsive and tractable system for evaluating therapeutic regimens for melanoma in an immunocompetent setting.

Original languageEnglish (US)
Pages (from-to)2007-2018.e6
JournalJournal of Investigative Dermatology
Volume143
Issue number10
DOIs
StatePublished - Oct 2023
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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