Programme

Tak W Mak

Princess Margaret Cancer Centre, University of Toronto and Centre of Oncology and Immunology, University of Hong Kong

Checkpoint inhibitors has accelerated the clinical implementation of a vast mosaic of single agents and combination immunotherapies. However, the lack of clinical translation for immunotherapies as monotherapies or in combination emphasized the importance of discerning investigation. Multiple molecular mechanisms, such as metabolic alteration, genomic instability and neural regulation converge to propel tumour development are engaged. Mutations in enzymes, such as IDH, gives rise to gliomas, leukemia (AML) and lymphoma (AITL). Another component is a seemingly unconnected biological process and immunity is genomic instability caused by inadequate DNA repair or excessive DNA damage. I will discus metabolic elements and genomic instability in immune cell regulation of infections, autoimmune diseases, thymic selection, liver regeneration and cancer development.

Hai Qi, Tsinghua University

Tak W Mak

Princess Margaret Cancer Centre, University of Toronto and Centre of Oncology and Immunology, University of Hong Kong

Crosstalk between the nervous system and the immune system shapes the tumor microenvironment. Cholinergic T cells, a unique population of TCR-induced, acetylcholine-producing T cells, have emerged as an integrative interface between these two fundamental body systems. Here we review the distinct characteristics and functions of cholinergic T cells in cancer settings. We first outline the expression of choline acetyltransferase and the cholinergic machinery in T cells. We then describe the dysfunctional state of ChAT-expressing T cells in cancer and delve into their modulatory effects on T cells, cancer cells, and the tumor microenvironment, including its populations of immune cells, its vasculature, and its nerves. We also discuss the clinical implications of harnessing the potential of cholinergic T cells and future directions for increasing our understanding of their importance and possible exploitation.

Wenwen Zeng, Tsinghua University

The peripheral nervous system serves as the crucial communication network linking the central nervous system to every part of the body, acting as a vast information superhighway for sensory and motor signals. A vital component of this system is the autonomic nervous system, which operates involuntarily to regulate our internal organ functions. It plays a particularly important role in controlling metabolic processes and maintaining the delicate energy balance of the body, essentially acting as the unseen manager of our physiological resources. By unraveling the intricate mechanisms of the autonomic nervous system, particularly the roles of the sympathetic branch, we have gained a deeper understanding of how our bodies masterfully adapt to conditions ranging from stress and exercise to fasting. This knowledge is critical for health outcomes. It enables targeted treatments for metabolic disorders like diabetes and obesity, and helps manage conditions driven by nervous system dysregulation. Ultimately, decoding this internal control system empowers us to develop interventions that enhance the innate resilience of the body, paving the way for more personalized and effective approaches to long-term wellness.

Burkhard Becher

University of Zurich

Cytokines are often cast as the villains of inflammatory disease. Molecules such as IL-23 and GM-CSF have emerged as central drivers of tissue inflammation and autoimmune pathology, and targeting these cytokines has transformed the treatment of chronic inflammatory diseases. In this seminar, I will begin by discussing how these “bad actors” orchestrate pathogenic immune circuits involving T cells and myeloid cells that fuel chronic inflammation. However, cytokine biology is rarely one-dimensional. I will present recent work revealing unexpected physiological roles for these same mediators. We find that IL-23 can enhance the suppressive capacity of regulatory T cells, strengthening mechanisms that restrain inflammation. In parallel, we discovered that GM-CSF sustains a specialized macrophage population in exocrine glands, which we termed adenophages, with roles in tissue homeostasis. These findings highlight the remarkable context-dependence of cytokine signaling and challenge simple pro- versus anti-inflammatory classifications.

Min Peng

School of Basic Medical Sciences, Tsinghua University

As living drugs, CAR T cells have cured some patients with B-cell malignancies and have the potential to cure chronic diseases that were traditionally considered incurable. To realize this potential, several key challenges remain, including the need for chemotherapeutic conditioning, achieving long-term functional persistence, and, above all, reducing the cost to an affordable level. Our goal is to address these challenges in T cell therapy using cutting-edge technologies and to expand the indications of T cell therapy from rare diseases to common chronic diseases such as asthma, diabetes, arthritis, and others. In addition, we are developing new platforms for the large-scale production of therapeutic T cells at low cost, with the hope that every patient in need will have access to and be able to afford such T cell therapies.

Morning Networking Break

Heidi GS Ling, The University of Hong Kong

In cancer, immune cells function as a double-edged sword: while CD8+ T cells drive anti-tumor immunity and form the foundation of cancer immunotherapy, innate immune cells such as neutrophils are often reprogrammed within the tumor microenvironment into pro-tumorigenic cells that suppress tumor-killing immune responses and act as a key barrier to treatment efficacy. Using liver cancer—a highly prevalent and aggressive tumor in Hong Kong—as a model, we investigate the factors within the tumor microenvironment that drive pro-tumorigenic neutrophil formation, dissect how these cells suppress immunotherapy, and test novel therapeutic targets to overcome this barrier. This highly translatable research will inform new strategies that specifically target pathogenic neutrophils while preserving conventional neutrophil populations essential for host defense. Such an approach could offer a safer and more effective therapeutic option for cancer patients.

Meng Michelle Xu, Tsinghua University

Prof. Philip Hei LI, University of Hong Kong

Morning networking break

Cheng-Lung Ku, Chang Gung University 

Anticytokine autoantibodies, which disrupt the functions of specific cytokines, are increasingly recognized as key drivers of human disease. Anti–interferon-γ autoantibodies (AIGAs), first identified in patients with mycobacterial infections, are now prevalent in Southeast Asia and Taiwan. Patients often present with salmonellosis, herpes zoster, or Talaromyces marneffei infections, marking AIGAs as a unique form of adult-onset immunodeficiency.

Similarly, anti–GM-CSF autoantibodies are now linked to cryptococcosis, while anti–type I interferon autoantibodies represent a major risk factor for life-threatening COVID-19 and other viral illnesses. Together, these findings highlight these autoantibodies as critical causes of opportunistic infections. In this discussion, I will address the clinical and immunological significance of these conditions, the underlying pathogenic mechanisms of the antibodies, and emerging therapeutic approaches.

Chak Sing Lau, The University of Hong Kong

Lai Guan Ng, Westlake University

Neutrophils are specialized cells of the early innate immune response. A long-standing question in the f ield of neutrophil research is whether a distinct subset of these cells truly exists, or different populations are merely a manifestation of the neutrophil maturation/polarization state. Lineage tracing techniques have been used to distinguish different subsets of myeloid cell types; however, more needs to be done with neutrophils. This talk will discuss how in-depth analysis of physiological and pathological granulopoiesis by multiomics and multiparametric technologies can contribute to better understanding neutrophil subsets and discover new functions.

Morning networking break