Basal immunity
Dietary Lactobacillus-derived exopolysaccharide enhances immune checkpoint blockade therapy
Cancer Discov. 2022 Feb 17;candisc.0929.2021.
Graduate School of Medicine, Juntendo University
Hirotaka Kawanabe-Matsuda
Our repertoire analysis was used in the study of combination therapy with immune checkpoint inhibitors. In an experiment in which lactic acid bacteria "Lactobacillus bulgaricus OLL1073R-1 extracellular polysaccharide (EPS-R1)" were ingested into cancer-bearing mice, how the intratumoral infiltrative lymphocytes changed depending on the presence or absence of anti-CTLA-4 antibody administration was evaluated. It was reported that the TCR repertoire clonality was significantly enhanced in the anti-CTLA-4 antibody- administered group compared to that in the non-administered group.

Basal immunity
DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus
iScience. 2021 Dec 2;25(1):103537.
Institute for Rheumatic Diseases
Shunichi Shiozawa
Our repertoire analysis was used in the study of autoimmune diseases. The paper evaluates the properties and origins of autoantibody-inducing CD4 T cells (aiCD4 T cells) using biochemical characterization, cell transplantation studies in mice, and quantification of cell numbers in peripheral blood and tissues of patients with systemic lupus erythematosus (SLE). The possibility of treating SLE with antibodies against these cells is also being investigated. Repertoire analysis has been used on mouse CD4 T cells. As a result, the DOCK8⁺Tfh cells (DOCK8-expressing T follicular helper cells) generated by external stimulation had limited diversity compared to unstimulated cells and were biased toward the new TCR repertoire.

Basal immunity
CD153-CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury
J Clin Invest. 2022 Jan 18;132(2):e146071.
Department of Nephrology, Graduate School of Medicine, Kyoto University
Yuki Sato
Our repertoire analysis was used in the study of immunosenescence. The paper suggests that the interaction of aging T cells (SAT) and aging B cells (ABC) via the CD153-CD30 signal is important in tertiary lymphoid tissue formation. It also suggests that by inhibiting the interaction, tertiary lymphatic tissue formation and renal dysfunction can be suppressed. Therefore, it has been shown that treatment methods targeting immune cells and the CD153-CD30 pathway may be useful in the treatment of kidney disease. Repertoire analysis was performed in detail for each cell fraction in the kidney and spleen of mice and used for similarity analysis.

Hematological malignancy
Clinical significance of the immunoglobulin G heavy-chain repertoire in peripheral blood mononuclear cells of adult T-cell leukaemia-lymphoma patients receiving mogamulizumab
Br J Haematol. 2022 Feb;196(3):629-638.
Cancer Center, Kumamoto University Hospital
Kisato Nosaka
Our repertoire analysis was used in the study of leukemia. The paper reports the results of BCR repertoire analysis using peripheral blood mononuclear cells (PBMC) before mogamulizumab administration in adult T-cell leukemia/lymphoma (ATL) patients. In the MIMOGA study, BCR analysis was performed in 81 patients because the low proportion of CD2^- CD19⁺ B cells in PBMC was a significant poor prognostic factor for overall survival (OS). The results showed that peripheral IgG B cells in ATL patients had limited repertoire compared to healthy subjects, and patients with a high diversity index had significantly longer OS than patients with a low diversity index. The results of the BCR repertoire analysis performed in this study indicate the importance of the humoral immune response in ATL patients treated with mogamulizumab. Our researchers are participating in this analysis as co-authors.

Solid tumor
Determining the immune environment of cutaneous T-cell lymphoma lesions through the assessment of lesional blood drops
Sci Rep. 2021 Oct 4;11(1):19629.
Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences
Kan Torii
Our repertoire analysis was used in the study of mycosis fungoides. The therapeutic effect of drug was examined using lesional blood drops of patients with cutaneous T-cell lymphoma. As a result of the analysis of CD8⁺ CD45RO⁺ T cells in the blood of the lesion using TCR repertoire analysis, a characteristic repertoire was shown. Analysis using this lesion blood may facilitate the evaluation of the therapeutic effect of skin inflammatory diseases.

Basal immunity
Regulation of the immune tolerance system determines the susceptibility to HLA-mediated abacavir-induced skin toxicity
Commun Biol. 2021 Sep 28;4(1):1137.
Laboratory of Cancer Biology and Immunology, Section of Host Defences, Institute of Natural Medicine, University of Toyama
Takeshi Susukida
Our repertoire analysis was used in the study of immune tolerance. The results of TCR repertoire analysis have been used for comparison with clinical features in studies using transgenic mice on abacavir-induced susceptibility to skin toxicity.

Clinical immunity
Th₁ - CD_11c⁺ B cell axis associated with response to plasmapheresis in multiple sclerosis
Ann Neurol. 2021 Oct;90(4):595-611.
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry
Kimitoshi Kimura
Our repertoire analysis was used in the study of multiple sclerosis. The paper reports that plasmapheresis reduced Th1 cell inflammation-related gene expression in patients with multiple sclerosis. Furthermore, when a repertoire analysis was performed on CD_11c⁺ B cells in which IFN-γ expression in Th1 cells is associated with several autoimmune diseases, it was reported that there was a positive correlation, and diversity was reduced.

Solid tumor
Tumor-infiltrating CD8⁺ T cells recognize a heterogeneously expressed functional neoantigen in clear cell renal cell carcinoma
Cancer Immunol Immunother. 2021 Sep 7. doi: 10.1007/s00262-021-03048-6.
Department of Pathology, Sapporo Medical University School of Medicine
Masahiro Matsuki
Our repertoire analysis was used in the study of solid tumors. The diversity of cancer cells in the tumor tissue, that is, "intra-tumor heterogeneity," is reported using the tumor tissue of patients with clear cell type renal cell carcinoma. As a result of microscopically dividing the tumor tissue into high-grade and low-grade sites and performing repertoire analysis, neoantigen-specific T cells were profiled from infiltrating lymphocytes in the high-grade sites, and neoantigen was also identified. However, it was not detected in the low-grade site. Similarly, it has been reported that the tumor microenvironment differs between tissues separated into microscopically high-grade and low-grade sites within the same tumor, showing "intratumor heterogeneity."