The inflammation-cancer nexus: Unlocking novel strategies for immunomodulation and therapy

The relationship between inflammation and cancer represents one of the central paradoxes in modern tumor immunology. On one hand, chronic inflammation is a well-established driver of tumorigenesis; on the other, immune activation forms the foundation of successful cancer immunotherapy. Recent research has uncovered a more intricate, bidirectional interplay: while patients receiving immune checkpoint inhibitors (ICIs) exhibit heightened susceptibility to infections, those who survive sepsis may develop long-lasting anti-tumor immunity—mediated by the "trained immunity" in macrophages.Although ICIs have revolutionized cancer treatment by improving outcomes across multiple solid tumors, their broader immunomodulatory effects are raising concerns, leading to a higher incidence of opportunistic infections—including tuberculosis, pneumococcal pneumonia, and invasive fungal diseases. In contrast, epidemiological studies reveal a surprising trend: survivors of sepsis exhibit a lower subsequent risk of developing cancer. This protective effect appears to be driven by reprogrammed innate immune responses, particularly through trained immunity in macrophages. This collection aims to investigate the intricate interplay between cancer and inflammation, highlighting the "double-edged sword" nature of the immune system. Given the limited availability of patients with cancer-associated sepsis, research in this field remains challenging. As such, we focus on two pivotal themes:1. Immune checkpoint inhibitor (ICI) therapy exerts anti-tumor effects by activating adaptive immunity, yet often at the expense of compromising innate immune defenses. What are the most recent advances in deciphering the complex molecular networks underlying immune imbalance following ICI treatment? Emerging insights from cutting-edge single-cell sequencing technologies and multi-omics analyses are beginning to unravel the dynamic crosstalk between immune cell subsets and regulatory pathways, offering a deeper understanding of treatment-related immune dysregulation.2. Conversely, sepsis-induced immune training reprograms the epigenetic and metabolic landscape of the innate immune system, conferring a durable anti-tumor "memory." Central to this trained immunity are modifications in epigenetic marks and shifts in key metabolic pathways. What are the promising clinical intervention strategies and therapeutic targets emerging from this phenomenon? This line of inquiry opens new avenues for drug development aimed at harnessing trained immunity to enhance cancer immunotherapy.We welcome submissions of original research, reviews, and perspective articles covering the following specific issues: • Mechanistic Insights: Leveraging single-cell multi-omics and advanced technologies to map the functional trajectories of specific immune cell subsets—such as neutrophils and mucosal-associated invariant T (MAIT) cells—during ICI therapy, and to dissect the spatiotemporal dynamics of tissue-resident memory (TRM) T cell–macrophage interactions in the context of sepsis training.• Clinical Translation: Designing prospective cohort studies to systematically evaluate the molecular underpinnings linking sepsis survival with reduced cancer risk, with the goal of informing and advancing clinical trials of personalized trained immunity-based immunotherapies.• Precision Immunotherapy: Developing innovative tools for detecting critical mechanistic mediators and immune cell subpopulations, alongside novel intervention strategies that enable precise temporal control over anti-tumor and anti-infective immunity—ultimately paving the way for safer, more effective immunotherapeutic approaches for patients facing cancer or infectious challenges.Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: JINGJING XU, Shisong Jiang, Karsten Haupt Source: https://www.frontiersin.org/research-topics/76198/the-inflammation-cancer-nexus-unlocking-novel-strategies-for-immunomodulation-and-therapy