Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LN). In contrast, percentages of CD8(+) T cells were unchanged and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein (gp)100-specific CD8(+) T cells were not deleted during tumor-development, as revealed by pentamer staining in skin and draining LN. They, however, were unresponsive to ex vivo gp100 peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSC) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSC) over monocytic MDSC (moMDSC). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS) and TGF-β and suppressed T cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.Journal of Investigative Dermatology accepted article preview online, 29 June 2015. doi:10.1038/jid.2015.241.