Ana Patrícia Gomes

Cancer progression is shaped not only by tumor-intrinsic programs and the local microenvironment but also by profound metabolic rewiring of the host at the organismal scale. Tumors engage in dynamic cross-talk with distant organs, immune and neuroendocrine networks, and systemic nutrient pools, generating a metabolically permissive macroenvironment that fuels tumor growth, supports metastatic dissemination, and undermines therapeutic efficacy. In this review, we synthesize emerging evidence showing how cancer-driven systemic metabolic remodeling reshapes glucose, lipid, and protein metabolism, perturbs immune and hematopoietic homeostasis, and hijacks neuroendocrine circuits governing energy balance and stress responses. We further highlight how these adaptations fuel cellular energetics within tumor cells as well as promote premetastatic niche formation, immune evasion, and therapy resistance, while leaving durable metabolic and inflammatory scars that accelerate biological aging and compromise long-term health in cancer survivors. Together, these findings position tumor–host metabolic cross-talk as a central, targetable axis in cancer biology with broad implications for therapy and survivorship care.

Supplementary Figure S8. CD4Th1 cytokine IFN-γ mediated changes on the chemokines, MHC class I and MHC class II antigen presentation-related genes in DCCs

Supplementary Figure S1. Gene expression profiles of DCCs

Supplementary Figure S12. IFN-γ regulates various signaling pathways in DCCs

Supplementary Figure S13. Intratumoral activation of anti-tumor CD4Th1 cells eradicate DCC and DCC driven metastasis.

Supplementary Figure S10. CD4Th1 cytokine IFN-γ regulates apoptosis and ISDS gene signatures in DCCs

Supplementary Figure S3. Immune profiling of tumor antigen targeting DC1 injected mammary gland and non- injected mammary gland

Supplementary Figure S2. Intratumoral activation of CD4Th1 cells delays primary tumor growth

Supplementary Figure S6. Phenotypic analysis of CD4 T cells in primary tumor, TDLN and metastatic site with DCCs

Supplementary Figure S5. The specificity and functional role of tumor antigen specific CD4Th1 cells and its effects on DCCs