Unveiling and targeting innate immune pathways in next-generation cancer therapy

Innate immunity is a cornerstone of the body’s immediate defense against cancer, orchestrating the early recognition and response to tumor cells through key players such as dendritic cells, macrophages, and natural killer (NK) cells. These cells utilize pattern recognition receptors (PRRs) to detect tumor-associated signals, setting off complex inflammatory cascades that can both suppress and promote tumor progression. While recent years have witnessed a surge of interest in immunotherapeutic strategies, the intricate mechanisms by which innate immunity interacts with tumor cells and shapes antitumor immunity remain only partially understood. Persistent challenges exist in unraveling how these initial immune responses can be leveraged to enhance cancer immunotherapy, as a full appreciation of their role in the tumor microenvironment and synergy with adaptive immunity is lacking. Cutting-edge studies have started to clarify the involvement of innate pathways, including NF-κB, STING, and inflammasomes, yet a comprehensive translation of this knowledge into effective, durable clinical interventions is still needed. This Research Topic aims to deepen our understanding of the mechanisms behind innate immune activation in cancer and to identify avenues for their therapeutic exploitation. A primary objective is to elucidate how innate immune pathways can be intentionally activated or modulated to potentiate antitumor responses, especially in tandem with existing immunotherapeutic agents. By evaluating the interplay between innate signaling and immune checkpoint inhibitors, targeted therapies, and oncolytic virus-based treatments, this research seeks to uncover new opportunities for overcoming immune resistance and improving patient outcomes. We are especially interested in research that maps novel signaling networks, deciphers mechanisms of immune cell recruitment and activation, and proposes innovative approaches for integrating innate immunity into multimodal cancer immunotherapy regimens.For this Research Topic, we encourage submissions that focus on the breadth and limitations of innate immune mechanisms as they relate specifically to cancer immunotherapy. Contributions may center on either fundamental mechanistic insights or translational strategies applicable to clinical care. To gather further insights in innate immune-based cancer treatments, we welcome articles addressing, but not limited to, the following themes:• Key signaling pathways of innate immunity in the context of cancer (e.g., PRRs, NF-κB, STING, inflammasomes)• Cellular mechanisms governing recruitment and activation of innate immune populations within the tumor microenvironment• Development and optimization of therapeutics designed to stimulate innate immune pathways• Innate immune modulation as a means of overcoming resistance to immune checkpoint blockade• Combined treatment modalities leveraging innate immune activation alongside targeted therapies and oncolytic virusesPlease 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: Rohit Upadhyay, Haitao Zhu, Cong Hu Source: https://www.frontiersin.org/research-topics/78895/unveiling-and-targeting-innate-immune-pathways-in-next-generation-cancer-therapy