Endocrine and Immunometabolic Control of the Tumor Microenvironment: Immune Infiltration, Crosstalk, and Response to Immunotherapy

Carcinogenesis arises from a convergence of genetic mutation, DNA damage, radiation, and environmental exposure. Advances in diagnostic and therapeutic markers have driven a steady decline in overall cancer mortality, yet advanced-stage disease remains difficult to manage because of treatment resistance, poor prognosis, and recurrence. A central driver of these clinical hurdles is the interplay between tumor heterogeneity and the tumor microenvironment (TME).The TME is an ecosystem of infiltrating immune cells, including T and B lymphocytes, macrophages and dendritic cells, together with stromal and endothelial components and the extracellular matrix. These populations shape tumor gene expression, molecular behavior, and therapeutic responsiveness, and they release cytokines and other mediators that either restrain or promote tumor growth and metastasis. Immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapies have reshaped oncology, but their efficacy in solid tumors remains limited by antigen heterogeneity, immunosuppressive niches, and systemic endocrine and metabolic dysregulation.What is less well resolved, and what this collection sets out to address, is the endocrine dimension of that problem. Systemic hormonal signals, local endocrine crosstalk within the tumor niche, and metabolic reprogramming of both tumor and immune compartments act as upstream determinants of immune infiltration and therapeutic resistance. Sex steroids, insulin and IGF signaling, adipokines, glucocorticoids, thyroid hormone, and neuroendocrine mediators all influence immune cell recruitment, differentiation, and exhaustion. Adiposity, insulin resistance, and nutrient competition further constrain effector function within the microenvironment. Understanding these axes is a prerequisite for extending immunotherapy to tumors that remain immunologically cold, and for explaining why response varies so widely between patients with comparable tumor genotypes.This Research Topic aims to elucidate how the TME, cellular heterogeneity, and endocrine or immunometabolic pathways intersect to shape disease outcomes, inform target identification, and influence responses to immunotherapy. We particularly welcome work on endocrine and hormone-dependent malignancies, and on the systemic endocrine and metabolic context of solid tumors more broadly.We welcome Original Research, Review, Mini-Review, and Perspective articles, including rigorous bioinformatics and multi-omics studies, on themes such as, but not limited to:• Endocrine and metabolic regulation of the TME: hormonal modulation of immune cell infiltration, nutrient competition, and immunometabolic crosstalk within the microenvironment.• Tumor heterogeneity and therapeutic resistance: the impact of inter- and intratumoral heterogeneity on immune evasion and on suboptimal responses to ICIs or CAR-T therapies.• Immune infiltration dynamics: mechanistic roles of infiltrating myeloid, lymphoid, and granulocytic lineages in driving or suppressing tumor progression.• Targeted interventions and checkpoint modulation: mechanisms of action of novel anti-cancer agents, checkpoint regulators, and combination strategies that reprogram the immunosuppressive TME.• Systemic endocrine context: obesity, insulin resistance, diabetes, and hormone therapy as modifiers of immunotherapy outcome. Topic editors: Muhammad Riaz Khan, Ranjha Khan Source: https://www.frontiersin.org/research-topics/86054/endocrine-and-immunometabolic-control-of-the-tumor-microenvironment-immune-infiltration-crosstalk-and-response-to-immunotherapy