Year: 2026
Type: review
Abstract: Immunotherapy has transformed cancer care, yet durable responses remain limited by mechanisms of resistance driven by tumors and their microenvironment. Midkine (MDK), a secreted heparin-binding growth factor, has recently emerged as a regulator of the cancer-immune interface. While MDK has long been recognized for its roles in cell survival, proliferation, and angiogenesis, new evidence highlights its ability to reprogram the tumor microenvironment by recruiting myeloid-derived suppressor cells, impairing T cell activation, and disrupting antigen presentation. MDK further reinforces immune evasion and therapeutic resistance through crosstalk with immune checkpoints, stromal components, and signaling pathways, including STAT3, PI3K/AKT, and the Wnt/β-catenin pathway. Here, we summarize current knowledge of MDK's immunoregulatory functions across various cancer types and propose a conceptual framework that positions MDK as a converging node linking oncogenic signaling with immune escape. We also discuss emerging translational strategies to inhibit MDK to overcome therapy resistance and enhance patient outcomes.
Source: iScience
Authors: Minakshi Saikia, Sai Prem, Vaishali Kapoor
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,240
OpenAlex ID: W7141065174