These data reveal key similarities and differences between the NeoAg-specific CD4+ T cell response within the tumor and draining lymph node throughout the course of tumor development, with the early appearance and increasing presence of Cltc-specific Tregs in both locations offering possible clues into how an initial Th1 response is followed by a potent population of NeoAg-specific regulatory cells. Here, CLTC is linked to neoplasm.