Department of Immuno genomic medicine

Introduction

Over a decade has elapsed since the approval of immune checkpoint inhibitors (ICIs), and their indications have been expanded to encompass a diverse array of cancer types. The long-term clinical outcomes have become evident. Despite the use of combined cancer immunotherapy including ICIs and various combination drugs, the rate of long-term survival is not sufficient, and a number of challenges have emerged. Concurrently, it has become evident that immune regulation is a pivotal factor in the carcinogenesis and progression of cancer. The objective of our research team is to investigate the reasons for the incomplete efficacy and transient nature of combined cancer immunotherapy. To this end, we have obtained samples from patients who have undergone the therapy and conducted comprehensive immune and genomic analyses of the tumor microenvironment using cutting-edge technologies. Our aim is to identify targets that can overcome resistance to treatment.

Technical Support

Department of Immuno-genomics Medicine was launched as a division of the Fundamental Innovative Oncology Core (FIOC), which was established to strengthen research collaboration at the National Cancer Center. We provide technical support for immunological analysis of the tumor microenvironment (multi-color flow cytometry, multiple immunohistochemistry, functional analysis using immune cells, etc) and gene expression analysis (RNA sequencing, single cell RNA/TCR sequencing, etc.) in various human tumor tissues including surgical specimens, biopsy specimens and body cavity fluid. Furthermore, we are engaged in spatial analysis for bispecific antibodies and antibody-drug conjugates.

Research Focus

The aim of our research projects is to analyze the effects of specific gene mutation and gene expression in cancer cells on the immunogenicity of cancer cells (endogenous changes) in the tumor microenvironment and the characteristics of immune cells/stromal cells infiltrating the tumor (exogenous changes). To achieve this, we are using pre- and post-treatment clinical specimens from various cancer types (especially gastrointestinal, lung, urological, head and neck, and skin cancers). We are searching for molecules involved in sensitivity or resistance to combined cancer immunotherapy. Furthermore, we analyze the functions of the identified target molecules in mouse models and propose their potential as new therapeutic targets.

1: The modulation of the tumor immune microenvironment by molecules expressed on the plasma membrane of cancer cells and the development of therapies targeting these molecules represent a promising avenue of research.

2：A pathophysiological analysis of immunosuppressive mechanisms by suppressive immune cell subsets, such as tumor-infiltrating myeloid cells.

3: Induction of immune activation in non-inflamed tumors with poor or eliminated immune cell infiltration.