Division of Translational Oncoimmunology

• Introduction
• Research topics
• Members
• Publications
• Education & Training

Introduction

Whether the immune system can recognize and eliminate nascent transformed cells that develop in the body, i.e., cancer immunosurveillance, has been debated for most of the 20th century. In 2001, Robert Schreiber revealed the existence of immunosurveillance in mouse (Shankaran V et al, Nature, 2001) and developed the concept of “cancer immunoediting” (Dunn GP et al, Nat Immunol, 2002). The process of cancer immunoediting consists of three phases: elimination, equilibrium, and escape. Accumulating data from basic research and latest comprehensive multi-omics analysis have demonstrated that immunoediting occurs not only in mice but also in humans.

Cancer immunotherapy was selected as the Breakthrough of the Year by Science magazine in 2013 for the development of immune checkpoint inhibitors (ICIs) and gene-engineered T cell immunotherapy. Dr. James P. Allison and Dr. Tasuku Honjo received the Nobel Prize in 2018 for the discovery and clinical application of ICIs. Cancer immunotherapy has attracted increased attention for cancer treatment, but ICIs remain effective only in a minority of patients. However, the efficacy of ICIs, which is characterized by durable responses that have never been seen before, has shown that host immunity, if re-activated, can eliminate cancer cells or maintain cancer in an equilibrium state (therapeutically induced cancer immune elimination or equilibrium).

Our laboratory is focused on understanding the molecular and cellular basis of natural and therapeutically induced cancer immunoediting in human. We will develop effective cancer immunotherapies combined with ICIs by collaborating with the Aichi Cancer Center Hospital.

Research topics

Understanding T cells and antigenic targets in cancer immunoediting

To improve the therapeutic efficacy of cancers, it is necessary to determine the mechanisms of naturally occurring and therapeutically induced cancer immune elimination or equilibrium in detail and develop immunotherapeutic strategies based on these mechanisms (Fig.1).
T cells are critical effecter immune cells in cancer elimination, and mutation-derived neoantigens are critical tumor antigens in natural responses to cancer in mice (Matsushita H et al, Nature, 2012). However, the underlying mechanisms are poorly understood, particularly in the human clinical setting, such as how many tumor antigens are related to cancer elimination, whether immunodominance of antigens exist in humans, and whether T cells recognizing neoantigens can control cancer for a long time. To address this, we utilize clinical samples including tumor tissues, lymph nodes, and peripheral blood, as well as clinical information from patients who underwent surgery/biopsy. We are focusing on adaptive CD4/CD8 T cells and tumor-specific neoantigens recognized by T cells. We also investigate immune responses induced by therapies such as ICIs to evaluate secondary cancer immunoediting.

Challenges to neoantigen identification using immunogenomic approaches

To identify the individual somatic mutations in whole exome/RNA sequencing data and predict candidate neoantigens derived from somatic mutations using in silico algorithm (Fig.2).
Immune responses against candidate MHC class I and II epitope peptides were confirmed by conventional cytokine assays, multimer staining, or TCR repertoire analysis using tumor-infiltrating T cells or peripheral blood mononuclear cells (PBMCs) from patients with cancer.
Particularly, we focus on the quality of neoantigens related to long-term survival. We will also determine whether long-lived memory CD4 and CD8 T cells against neoantigens exist in the peripheral blood in long-term responder patients upon treatment with ICIs.

Patient selection and biomarkers for cancer immunotherapy

To select patients who may benefit from cancer immunotherapy, we are comprehensively examining immune responses to cancer by evaluating immune-related gene expression and conducting immunohistochemistry analyses. We evaluate the “cancer immunogram” based on the understanding of cancer-immune interactions to determine the selection criteria for cancer vaccines (Fig.3).
We will evaluate and compare the immune statuses of long-termed responder, short-term responder, and non-responder cases treated with ICIs to understand the immune resistance mechanisms such as antigen loss, antigen presentation machinery (APM) defect, IFN insensitivity, expression of immune checkpoint molecules, oncogene-driven immune suppression, etc.

Development of cancer immunotherapy targeting neoantigens

In 2017, the results of two independent clinical trials of peptide or RNA vaccine therapies targeting neoantigens were reported in malignant melanoma (Ott PA et al, Nature, 2017; Sahin U et al, Nature, 2017). In the future, additional clinical trials of cancer vaccines targeting neoantigens are expected. Future challenges include improving neoantigen identification methods and developing a sensitive assay system for detecting neoantigens as well as determining patient selection criteria for the cancer vaccine. We will work to solve these problems by collaborating with the Aichi Cancer Center Hospital.

Members

Publications

1. Masago K, Kuroda H, Takahashi Y, Oya Y, Sasaki E, Sakakura N, Matsushita H. Synchronous driver gene alterations (EGFR L858R, T790M, and ROS1) rearrangements in a patient with early-stage lung adenocarcinoma. Cancer Genet. 268-269:124-127. 2022
2. Masago K, Kuroda H, Sasaki E, Fujita S, Shinohara S, Sugita Y, Takahashi Y, Matsushita H. Association of the KRAS genotype and clinicopathologic findings of resected non-small-cell lung cancer: A pooled analysis of 179 patients. Cancer Genet. 268-269:64-74. 2022 
3. Masago K, Kuroda H, Fujita S, Sasaki E, Takahashi Y, Shinohara S, Matsushita H. Biological difference between L858R and exon 19 deletion contributes to recurrence-free survival of resected non-small cell lung cancer. Oncology. 2022 Sep 13.
4. Muraoka D, Harada N, Shiku H, Akiyoshi K. Self-assembled polysaccharide nanogel delivery system for overcoming tumor immune resistance. J Control Release. 347:175-182. 2022
5. Dotsu Y, Muraoka D, Ogo N, Sonoda Y, Yasui K, Yamaguchi H, Yagita H, Mukae H, Asai A, Ikeda H. Chemical augmentation of mitochondrial electron transport chains tunes T cell activation threshold in tumors. J Immunother Cancer. 10(2):e003958. 2022
6. Sato S, Matsushita H, Shintani D, Kobayashi Y, Fujieda N, Yabuno A, Nishikawa T, Fujiwara K, Kakimi K, Hasegawa K. Association between effector-type regulatory T cells and immune checkpoint expression on CD8+ T cells in malignant ascites from epithelial ovarian cancer. BMC Cancer. 22(1):437. 2022 
7. Shinohara S, Takahashi Y, Komuro H, Matsui T, Sugita Y, Demachi-Okamura A, Muraoka D, Takahara H, Nakada T, Sakakura N, Masago K, Miyai M, Nishida R, Shomura S, Shigematsu Y, Hatooka S, Sasano H, Watanabe F, Adachi K, Fujinaga K, Kaneda S, Takao M, Ohtsuka T, Yamaguchi R, Kuroda H, Matsushita H. New evaluation of the tumor immune microenvironment of non-small cell lung cancer and its association with prognosis. J Immunother Cancer. 10(4):e003765. 2022
8. Masago K, Fujita S, Oya Y, Takahashi Y, Matsushita H, Sasaki E, Kuroda H. Comparison between Fluorimetry (Qubit) and Spectrophotometry (NanoDrop) in the Quantification of DNA and RNA Extracted from Frozen and FFPE Tissues from Lung Cancer Patients: A Real-World Use of Genomic Tests. Medicina (Kaunas). 57(12):1375. 2021
9. Kuroda H, Ichinose J, Masago K, Takahashi Y, Nakada T, Nakao M, Okumura S, Hashimoto K, Matsuura Y, Sakakura N, Matsushita H, Mun M. Permissible Outcomes of Lobe-Specific Lymph Node Dissection for Elevated Carcinoembryonic Antigen in Non-Small Cell Lung Cancer. Medicina (Kaunas). 57(12):1365. 2021 
10. Yoshikawa T, Wu Z, Inoue S, Kasuya H, Matsushita H, Takahashi Y, Kuroda H, Hosoda W, Suzuki S, Kagoya Y. Genetic ablation of PRDM1 in antitumor T cells enhances therapeutic efficacy of adoptive immunotherapy. Blood 139(14):2156-2172. 2022
11. Kuroda H, Masago K, Takahashi Y, Fujita S, Sasaki E, Nakada T, Sakakura N, Nakanishi H, Matsushita H, Yatabe Y. Positive Correlation Between the Number of Circulating Tumor Cells in the Pulmonary Vein and Tumor Spread Through Air Spaces in Resected Non-small Cell Lung Cancer. Anticancer Res. 41(11):5499-5505. 2021
12. Kuroda H, Takahashi Y, Shirai S, Takahara H, Nakada T, Sakakura N, Matsushita H. Survival benefit of immune checkpoint inhibitor monotherapy in patients with non-small cell lung cancer recurrence after completely pulmonary resection. Ann Transl Med. 9(15):1225. 2021
13. Nishida M, Yamashita N, Ogawa T, Koseki K, Warabi E, Ohue T, Komatsu M, Matsushita H, Kakimi K, Kawakami E, Shiroguchi K, Udono H. Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes. J Immunother Cancer. 9(9):e002954. 2021 
14. Kuroda H, Sugita Y, Masago K, Takahashi Y, Nakada T, Sasaki E, Sakakura N, Yamaguchi R, Matsushita H, Hida T. Clinical Guideline-Guided Outcome Consistency for Surgically Resected Stage III Non-Small Cell Lung Cancer: A Retrospective Study. Cancers (Basel).13(11):2531. 2021
15. Shigenobu T, Takahashi Y, Masugi Y, Hanawa R, Matsushita H, Tajima A, Kuroda H. Micropapillary Predominance Is a Risk Factor for Brain Metastasis in Resected Lung Adenocarcinoma. Clin Lung Cancer. S1525-7304(21)00085-1. 2021
16. Sato Y, Mori K, Hirano K, Yagi K, Kobayashi Y, Nagaoka K, Hosoi A, Matsushita H, Kakimi K, Seto Y. Adoptive γδT-cell transfer alone or combined with chemotherapy for the treatment of advanced esophageal cancer. Cytotherapy. 23(5):423-432. 2021
17. Takahashi Y, Suzuki S, Hamada K, Nakada T, Oya Y, Sakakura N, Matsushita H, Kuroda H. Sarcopenia is poor risk for unfavorable short- and long-term outcomes in stage I non-small cell lung cancer. Ann Transl Med. 9(4):325. 2021
18. Matsui T, Takahashi Y, Nakada T, Matsushita H, Oya Y, Sakakura N, Kuroda H. Efficacy of Xenon Light With Indocyanine Green for Intersegmental Visibility in Thoracoscopic Segmentectomy. J Surg Res.259:39-46. 2021
19. Yabuno A, Matsushita H, Hamano T, Tan TZ, Shintani D, Fujieda N, Tan DSP, Huang RY, Fujiwara K, Kakimi K, Hasegawa K. Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma. .Sci Rep. 10(1):18503. 2020
20. Sato Y, Wada I, Odaira K, Hosoi A, Kobayashi Y, Nagaoka K, Karasaki T, Matsushita H, Yagi K, Yamashita H, Fujita M, Watanabe S, Kamatani T, Miya F, Mineno J, Nakagawa H, Tsunoda T, Takahashi S, Seto Y, Kakimi K.Integrative immunogenomic analysis of gastric cancer dictates novel immunological classification and the functional status of tumor-infiltrating cells. Clin Transl Immunology. 9(10):e1194. 2020
21. Kakimi K, Matsushita H, Masuzawa K, Karasaki T, Kobayashi Y, Nagaoka K, Hosoi A, Ikemura S, Kitano K, Kawada I, Manabe T, Takehara T, Ebisudani T, Nagayama K, Nakamura Y, Suzuki R, Yasuda H, Sato M, Soejima K, Nakajima JAdoptive transfer of zoledronate-expanded autologous Vγ9Vδ2 T-cells in patients with treatment-refractory non-small-cell lung cancer: a multicenter, open-label, single-arm, phase 2 study. J Immunother Cancer.;8(2):e001185. 2020
22. Matsushita H, Hasegawa K, Oda K, Yamamoto S, Asada K, Karasaki T, Yabuno A, Nishijima A, Nejo T, Kobayashi Y, Sato S, Ikeda Y, Miyai M, Takahashi Y, Yamaguchi R, Fujiwara K, Aburatani H, Kakimi K. Neoantigen load and HLA-class I expression identify a subgroup of tumors with a T cell-inflamed phenotype and favorable prognosis in homologous recombination-proficient high-grade serous ovarian carcinoma. J Immunother Cancer. 8(1):e000375. 2020
23. Kobayashi Y, Yamada D, Kawai T, Sato Y, Teshima T, Yamada Y, Nakamura M, Suzuki M, Matsumoto A, Nakagawa T, Hosoi A, Nagaoka K, Karasaki T, Matsushita H, Kume H, Kakimi K. Different immunological effects of the molecular targeted agents sunitinib, everolimus and temsirolimus in patients with renal cell carcinoma. Int J Oncol. 56(4):999-1013. 2020
24. Nejo T, Matsushita H, Karasaki T, Nomura M, Saito K, Tanaka S, Takayanagi S, Hana T, Takahashi S, Kitagawa Y, Koike T, Kobayashi Y, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Narita Y, Nagane M, Ueki K, Nishikawa R, Aburatani H, Mukasa A, Saito N, Kakimi K. Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma. Cancer Immunol Res. 7(7):1148-1161. 2019
25. Ohue Y, Kurose K, Karasaki T, Isobe M, Yamaoka T, Futami J, Irei I, Masuda T, Fukuda M, Kinoshita A, Matsushita H, Shimizu K, Nakata M, Hattori N, Yamaguchi H, Fukuda M, Nozawa R, Kakimi K, Oka M. Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti-Programmed Cell Death-1 Therapy in NSCLC. J Thorac Oncol. 14(12):2071-2083. 2019
26. Emoto K, Eguchi T, Tan KS, Takahashi Y, Aly RG, Rekhtman N, Travis WD, Adusumilli PS. Expansion of the Concept of Micropapillary Adenocarcinoma to Include a Newly Recognized Filigree Pattern as Well as the Classical Pattern Based on 1468 Stage I Lung Adenocarcinomas. J Thorac Oncol 14(11):1948-1961. 2019
27. Aly RG, Rekhtman N, Li X, Takahashi Y, Eguchi T, Tan KS, Rudin CM, Adusumilli PS, Travis WD. Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung. J Thorac Oncol 14(9):1583-1593. 2019
28. Takahashi Y, Suzuki S, Matsutani N, Kawamura M. 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the evaluation of clinically node-negative non-small cell lung cancer. Thorac Cancer 10(3):413-420. 2019
29. Kataoka K, Miyoshi H, Sakata S, Dobashi A, Couronne L, Kogure Y, Sato Y, Nishida K, Gion Y, Shiraishi Y, Tanaka H, Chiba K, Watatani Y, Kakiuchi N, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Sanada M, Onozawa M, Teshima T, Yoshiki Y, Ishida T, Suzuki K, Shimada K, Tomita A, Kato M, Ota Y, Izutsu K, Demachi-Okamura A, Akatsuka Y, Miyano S, Yoshino T, Gaulard P, Hermine O, Takeuchi K, Ohshima K, Ogawa S. Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas.　 Leukemia. 33(7):1687-1699. 2019
30. Ohta R, Demachi-Okamura A, Akatsuka Y, Fujiwara H, Kuzushima K. Improving TCR affinity on 293T cells. J Immunol Methods. 466:1-8. 2019
31. Imai Y, Hasegawa K, Matsushita H, Fujieda N, Sato S, Miyagi E, Kakimi K, Fujiwara K. Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma. Oncol Lett. 15(5):6457-6468. 2018
32. Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T, Saito T, Matsushita H, Uchida E, Seto Y, Goldenring JR, Kakimi K, Tatematsu M, Tsukamoto T.　Established gastric cancer cell lines transplantable into C57BL/6 mice demonstrate FGFR4 promotion of tumor growth.　Cancer Sci. 109(5):1480-1492. 2018.
33. Nagaoka K, Hosoi A, Iino T, Morishita Y, Matsushita H, Kakimi K. Dendritic cell vaccine induces antigen-specific CD8+ T cells that are metabolically distinct from those of peptide vaccine and is well-combined with PD-1 checkpoint blockade. Oncoimmunology. 7(3):e1395124. 2017
34. Hosoi A, Takeda K, Nagaoka K, Iino T, Matsushita H, Ueha S, Aoki S, Matsushima K, Kubo M, Morikawa T, Kitaura K, Suzuki R, Kakimi K. Increased diversity with reduced “diversity evenness” of tumor infiltrating T-cells for the successful cancer immunotherapy. Sci Rep. 8(1):1058. 2018
35. Hoshikawa M, Aoki T, Matsushita H, Karasaki T, Hosoi A, Odaira K, Fujieda N, Kobayashi Y, Kambara K, Ohara O, Arita J, Hasegawa K, Kakimi K, Kokudo N.NK cell and IFN signatures are positive prognostic biomarkers for resectable pancreatic cancer. Biochem Biophys Res Commun. 495(2):2058-2065. 2018
36. Matsushita H, Hasegawa K, Oda K, Yamamoto S, Nishijima A, Imai Y, Asada K, Ikeda Y, Karasaki T, Fujiwara K, Aburatani H, Kakimi K. The frequency of neoantigens per somatic mutation rather than overall mutational load or number of predicted neoantigens per se is a prognostic factor in ovarian clear cell carcinoma. Oncoimmunology. 6(8):e1338996. 2017
37. Aoki T, Matsushita H, Hoshikawa M, Hasegawa K, Kokudo N, Kakimi K. Adjuvant combination therapy with gemcitabine and autologous γδ T-cell transfer in patients with curatively resected pancreatic cancer. Cytotherapy. 19(4):473-485. 2017
38. Karasaki T, Nagayama K, Kuwano H, Nitadori JI, Sato M, Anraku M, Hosoi A, Matsushita H, Morishita Y, Kashiwabara K, Takazawa M, Ohara O, Kakimi K, Nakajima J. An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer. J Thorac Oncol. 12(5):791-803. 2017
39. Karasaki T, Nagayama K, Kuwano H, Nitadori JI, Sato M, Anraku M, Hosoi A, Matsushita H, Takazawa M, Ohara O, Nakajima J, Kakimi K. Prediction and prioritization of neoantigens: integration of RNA sequencing data with whole-exome sequencing. Cancer Sci. 108(2):170-177. 2017
40. Odaira K, Kimura SN, Fujieda N, Kobayashi Y, Kambara K, Takahashi T, Izumi T, Matsushita H, Kakimi K. CD27(-)CD45(+) γδ T cells can be divided into two populations, CD27(-)CD45(int) and CD27(-)CD45(hi) with little proliferation potential. Biochem Biophys Res Commun. 478(3):1298-303. 2016
41. Matsushita H, Sato Y, Karasaki T, Nakagawa T, Kume H, Ogawa S, Homma Y, Kakimi K. Neoantigen load, antigen presentation machinery, and immune signatures determine prognosis in clear cell renal cell carcinoma. Cancer Immunol Res. 4(5): 463-71. 2016
42. Makise N, Morikawa T, Nakagawa T, Ichimura T, Kawai T, Matsushita H, Kakimi K, Kume H, Homma Y, Fukayama M. MAGE-A expression, immune microenvironment, and prognosis in upper urinary tract carcinoma. Hum Pathol. 50:62-9. 2016
43. Karasaki T, Nagayama K, Kawashima M, Hiyama N, Murayama T, Kuwano H, Nitadori JI, Anraku M, Sato M, Miyai M, Hosoi A, Matsushita H, Kikugawa S, Matoba R, Ohara O, Kakimi K, Nakajima J.　Identification of Individual Cancer-Specific Somatic Mutations for Neoantigen-Based Immunotherapy of Lung Cancer. J Thorac Oncol. 11(3):324-333. 2015
44. Matsushita H, Hosoi A, Ueha S, Abe J, Fujieda N, Tomura M, Maekawa R, Matsushima K, Ohara O, Kakimi K. Cytotoxic T lymphocytes block tumor growth both by lytic activity and IFNγ-dependent cell-cycle arrest. Cancer Immunol Res. Jan;3(1):26-36. 2015
45. Futami J, Nonomura H, Kido M, Niidoi N, Fujieda N, Hosoi A, Fujita K, Mandai K, Atago Y, Kinoshita R, Honjo T, Matsushita H, Uenaka A, Nakayama E, Kakimi K. Sensitive Multiplexed Quantitative Analysis of Autoantibodies to Cancer Antigens with Chemically S-Cationized Full-Length and Water-Soluble Denatured Proteins. Bioconjug Chem. 26(10):2076-84. 2015
46. Miyai M, Eikawa S, Hosoi A, Iino T, Matsushita H, Isobe M, Uenaka A, Udono H, Nakajima J, Nakayama E, Kakimi K. Detection and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB) Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient. PLoS One. Aug 20;10(8):e0136086. 2015
47. Hirano K, Hosoi A, Matsushita H, Iino T, Ueha S, Matsushima K, Seto Y, Kakimi K. The nitric oxide radical scavenger carboxy-PTIO reduces the immunosuppressive activity of myeloid-derived suppressor cells and potentiates the antitumor activity of adoptive cytotoxic T lymphocyte immunotherapy. Oncoimmunology. 4(8). 2015.
48. Futami J, Fujiyama H, Kinoshita R, Nonomura H, Honjo T, Tada H, Matsushita H, Abe Y, Kakimi K. Denatured Mammalian protein mixtures exhibit unusually high solubility in nucleic Acid-free pure water. PLoS One. 9(11):e113295. 2014
49. Yamada D, Matsushita H, Azuma T, Nakagawa T, Nagata M, Yamada Y, Suzuki M, Fujimura T, Fukuhara H, Kume H, Homma Y, Kakimi K. Granulocyte macrophage colony-stimulating factor as a predictor of the response of metastatic renal cell carcinoma to tyrosine kinase inhibitor therapy. Mol Clin Oncol. 2(6):1023-1027. 2014
50. Matsushita H, Enomoto H, Kume H, Nakagawa T, Fukuhara H, Suzuki M, Fujimura T, Homma Y and Kakimi K. A pilot study of autologous tumor lysate-loaded dendritic cell vaccination combined with sunitinib for metastatic renal cell carcinoma. Journal for Immunotherapy of Cancer 2:30. 2014
51. Kawai T, Enomoto Y, Morikawa T, Matsushita H, Kume H, Fukayama M, Yamaguchi H, Kakimi K, Homma Y. High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy.Mol Clin Oncol. 2(1):38-42. 2014
52. Wada I, Matsushita H, Noji S, Mori K, Yamashita H, Nomura S, Shimizu N, Seto Y, Kakimi K. Intraperitoneal injection of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer. Cancer Med. 3(2):362-75. 2014
53. Wada H, Isobe M, Kakimi K, Mizote Y, Eikawa S, Sato E, Takigawa N, Kiura K, Tsuji K, Iwatsuki K, Yamasaki M, Miyata H, Matsushita H, Udono H, Seto Y, Yamada K, Nishikawa H, Pan L, Venhaus R, Oka M, Doki Y, Nakayama E.Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen. J Immunother. 37(2):84-92. 2014
54. Ichimura T, Morikawa T, Kawai T, Nakagawa T, Matsushita H, Kakimi K, Kume H, Ishikawa S, Homma Y, Fukayama M. Prognostic significance of CD204-positive macrophages in upper urinary tract cancer. Ann Surg Oncol. Jun;21(6):2105-12. 2014
55. Hosoi A, Matsushita H, Shimizu K, Fujii S, Ueha S, Abe J, Kurachi M, Maekawa R, Matsushima K, Kakimi K. Adoptive cytotoxic T lymphocyte therapy triggers a counter-regulatory immunosuppressive mechanism via recruitment of myeloid-derived suppressor cells. Int J Cancer. Apr 15;134(8):1810-22. 2014
56. Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K. Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain and the common γ-chain. Cytotherapy. Apr;15(4):481-91. 2013
57. Shimizu K, Mizuno T, Shinga J, Asakura M, Kakimi K, Ishii Y, Masuda K, Maeda T, Sugahara H, Sato Y, Matsushita H, Nishida K, Hanada K, Dorrie J, Schaft N, Bickham K, Koike H, Ando T, Nagai R, Fujii S. Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells.Cancer Res. Jan 1;73(1):62-73. 2013
58. Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, Arthur CD, White JM, Chen YS, Shea LK, Hundal J, Wendl MC, Demeter R, Wylie T, Allison JP, Smyth MJ, Old LJ, Mardis ER, Schreiber RD. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 482(7385): 400-4. 2012
59. Noji S, Hosoi A, Takeda K, Matsushita H, Morishita Y, Seto Y, Kakimi K. Targeting spatiotemporal expression of CD137 on tumor-infiltrating cytotoxic T lymphocytes as a novel strategy for agonistic antibody therapy. J Immunother. Jul;35(6):460-72. 2012
60. Kondo M, Izumi T, Fujieda N, Kondo A, Morishita T, Matsushita H, Kakimi K. Expansion of Human Peripheral Blood γδ T Cells using Zoledronate. J Vis Exp. Sep 9 ;(55) pii:3182. 2011
61. Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, Lee H, Arthur CD, White JM, Kalinke U, Murphy KM, Schreiber RD. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 208(10):1989-2003. 2011
62. Sakamoto M, Nakajima J, Murakawa T, Fukami T, Yoshida Y, Murayama T, Takamoto S, Matsushita H, Kakimi K. Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded γδTcells: a phase I clinical study. J Immunother. Mar;34(2):202-11. 2011
63. Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, and Murphy KM. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science. 322, 1097-1100. 2008
64. Ishida T, Obata Y, Ohara N, Matsushita H, Sato S, Uenaka A, Saika T, Miyamura T, Chayama K, Nakamura Y, Wada H, Yamashita T, Morishima T, Old LJ, Nakayama E .Identification of the HERV-K gag antigen in prostate cancer by SEREX using autologous patient serum and its immunogenicity. Cancer Immun. 8:15. 2008

Education & Training

We are always recruiting researchers from inside or outside of Japan. To develop effective cancer immunotherapies, we would like to work with young students or postdocs who have shown research abilities and the ability to perform in collaborative projects within a team. Good communication skills and an enthusiastic personality are expected.
Our laboratory is a part of the Nagoya University Graduate School of Medicine. Please follow this link:Graduate Programs

Recruitment Announcement

• Research Resident