TY - JOUR
T1 - A Spontaneous Melanoma Mouse Model Applicable for a Longitudinal Chemotherapy and Immunotherapy Study
AU - Eddy, Kevinn
AU - Gupta, Kajal
AU - Pelletier, Jeffrey C.
AU - Isola, Allison L.
AU - Marinaro, Christina
AU - Rasheed, Maryam Abdur
AU - Campagnolo, Joseph
AU - Eddin, Mohamad Naser
AU - Rossi, Marco
AU - Fateeva, Anna
AU - Reuhl, Kenneth
AU - Shah, Raj
AU - Robinson, Ann K.
AU - Chaly, Anna
AU - Freeman, Katie B.
AU - Chen, Wenjin
AU - Diaz, Jesus
AU - Furmanski, Philip
AU - Silk, Ann W.
AU - Reitz, Allen B.
AU - Zloza, Andrew
AU - Chen, Suzie
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jid.2023.03.1664
DO - 10.1016/j.jid.2023.03.1664
M3 - Article
C2 - 36997110
AN - SCOPUS:85165714746
SN - 0022-202X
VL - 143
SP - 2007-2018.e6
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 10
ER -