Immunotherapy Resistance and Chronic Inflammation

Inflammation, crucial for defending the host, activates immune and non-immune cells to combat pathogens and aid tissue repair. Though typically resolving post-threat, various factors can induce chronic inflammation, disrupting immune balance and heightening disease risks such as autoimmune diseases, cancer, and metabolic syndrome. Depending on the inflammatory immune cell and humoral factors, cancers can be divided into cold and hot. For example, cold tumors have low pro-inflammatory cytokines and leukocytes along with higher downstream signaling associated with immune checkpoints inducing T cell exhaustion and immunosuppression. Different immunotherapeutic approaches are needed depending on the immune micromilieu of the tumor. Achieving immune system reprogramming for sustained homeostasis represents a pivotal goal in treating these conditions. Recent years have seen immunotherapies revolutionize cancer and autoimmune therapy, aiming to enhance immune responses in cancer and mitigate excessive Immune activation in autoimmunity. Despite their promise, challenges persist in understanding why some patients exhibit poor or short-lived responses to immunotherapy, often due to evolving resistance mechanisms leading to disease recurrence.

This research topic aims to address the challenges associated with immune system reprogramming for sustained homeostasis, notably in the realm of chronic inflammation, encompassing conditions like cancer and autoimmune diseases. Recent years have witnessed rapid advancements in immunotherapy, offering promising avenues for therapeutic intervention. However, a significant hurdle persists in understanding why many patients fail to respond adequately to immunotherapy or experience short-lived benefits, often leading to disease recurrence driven by evolving resistance mechanisms. Resistance to immunotherapy is a multifaceted issue, influenced by various factors. A comprehensive understanding of these mechanisms is paramount for the development of more effective immunotherapeutic strategies and the enhancement of patient outcomes.

This Research Topic invites Original Research and Review Articles focusing on the following subtopics:

1. Exploring the hurdles encountered in the development and implementation of immunotherapeutic strategies for various chronic inflammatory diseases, including cancer and autoimmune conditions.
2. Understanding the intricate interplay between the gut microbiota and the immune system, and how microbial composition influences the efficacy and response to immunotherapies.
3. Genetic, epigenetic, and metabolic (systemic, cancer, and immune cell specific or immunometabolism) reprogramming influencing the response of cancer and chronic inflammatory patients to immunotherapies.
4. Unravelling the complex mechanisms, intrinsic and extrinsic, that drive resistance to cancer immunotherapies.
5. Novel adjuvants and combinatorial approaches for immunotherapies.
6. Role of circadian rhythm in regulating the efficacy of immunotherapies including vaccines.


Note that Sushmita Chakraborty is the Co-founder and Director of Proteinno Mab Tech. Additionally, please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.