암 면역학/생리학 연구실

Laboratory of Cancer Immunophysiology (LCI) 

College of Pharmacy, Pusan National University 

 

The Laboratory of Cancer Immunophysiology (LCI) investigates the immunological underpinnings of tumor progression and therapy resistance, with a mission to reprogram the tumor immune microenvironment (TIME) to support durable and systemic anti-cancer immunity. By integrating tools from immunoengineering, nanomedicine, cancer biology, and translational pharmacology, we aim to develop innovative therapeutic platforms that overcome immune exclusion, therapeutic refractoriness, and tumor heterogeneity. Our research prioritizes highly immunosuppressive solid tumors, including colorectal cancer and metastatic models, where current immunotherapies often fail.

1) Vascular Remodeling and Immunoperfusion Strategies

Previous studies from LCI have established the rationale for targeting cancer-associated thrombosis (CAT) to improve tumor perfusion. Using oral heparin derivatives, we demonstrated that anticoagulant therapy could alleviate hypoxia and enhance the delivery and efficacy of immune checkpoint inhibitors. However, CAT represents only one facet of the physical and biochemical barriers that limit immunotherapy efficacy. Building upon this foundation, our current research explores broader vascular remodeling strategies to reengineer tumor perfusion dynamics. We investigate the use of targeted fibrinolytics, VEGF-normalization agents, and hypoxia-responsive nanocarriers to overcome interstitial hypertension and vascular collapse. Recent findings underscore the therapeutic potential of combining perfusion-enhancing agents with immune checkpoint blockade to potentiate T cell infiltration and activation. Our ongoing work seeks to identify pharmacologic and biomaterial-based interventions that remodel aberrant tumor vasculature while preserving vascular integrity and promoting immune accessibility. 

2) Immunoengineering with Protein Nanocarriers 

LCI previously contributed to the field through the development of ferritin-based nanocages displaying high-affinity SIRPα variants, which effectively antagonize the CD47-SIRPα checkpoint and enhance macrophage-mediated phagocytosis. While effective in preclinical models, protein nanocarriers are now being reimagined to enable combinatorial immunomodulation beyond checkpoint inhibition alone. Current projects aim to develop multifunctional nanocarriers that integrate tumor-specific recognition, controlled immune stimulation, and dynamic payload release. Inspired by recent advances in synthetic immunology, we are constructing modular nanocages capable of co-delivering phagocytosis agonists, STING ligands, and tumor-associated antigens. These hybrid platforms are designed to initiate both innate and adaptive responses by synchronizing antigen presentation with inflammatory signaling within the tumor niche. In parallel, we are exploring albumin-binding immune conjugates and scaffolded cytokine delivery systems for controlled spatiotemporal immunoactivation. 

3) Harnessing Immunogenic Cell Death and Ferroptosis 

To address the challenge of non-immunogenic or “cold” tumors, our laboratory develops therapeutic modalities that transform cancer cell death into a source of endogenous vaccination. We continue to refine a peptide–drug conjugate (PDC) strategy that selectively activates in response to tumor-specific apoptotic cues, driving local immunogenic cell death (ICD) with minimal systemic toxicity. The conjugate enhances antigen cross-presentation and primes tumor-specific cytotoxic T lymphocytes. In parallel, we are pioneering strategies to harness ferroptosis—a form of regulated necrosis characterized by lipid peroxidation—for its potent immunogenicity. Recent studies have highlighted ferroptotic cells as unique triggers of dendritic cell activation and CD8+ T cell priming. We are now developing ferroptosis-inducing prodrugs and nanocarriers that amplify reactive oxygen species and lipid peroxides within tumor tissues, testing their synergy with checkpoint blockade and antigen presentation enhancers. 

4) Engineering Tertiary Lymphoid Structures (TLS) 

Our central research axis focuses on the de novo induction of tertiary lymphoid structures (TLS) in immunotherapy-resistant tumors. TLSs are lymph node-like immune aggregates that arise within non-lymphoid tissues and support in situ priming of adaptive immune responses. Their presence has been strongly correlated with clinical benefit across multiple cancer types. LCI explores diverse platforms for TLS induction, including: •Stromal-targeted nanoconjugates •Microbiome-engineered priming •mRNA nanocarriers Our work seeks to architect immune-reactive tumor ecosystems that self-sustain antigen presentation, T/B cell activation, and memory formation—laying the groundwork for long-term immunological control of solid tumors.

Research Vision