Annual Report 2020
Division of Innovative Pathology and Laboratory Medicine (Kashiwa Campus)
Genichiro Ishii, Nobuo Kuninaka, Hiroko Hashimoto
Introduction
The Division of Innovative Pathology and Laboratory Medicine was established at the Exploratory Oncology Research and Clinical Trial Center (EPOC) in 2016. Most of the members are from the Department of Pathology and Clinical Laboratories and Department of Clinical Laboratories in the National Cancer Center Hospital East (NCCHE).
Our goal is to provide a foundation for elucidating of cancer biology and its drug susceptibility by linking a wealth of clinical, biological, and morphological information to histopathological specimen information.
The Team and What We Do
Our members perform the following missions: 1) Promotion of translational research using quality-controlled specimens, 2) Clinical resident training for diagnosis and translational research, and 3) Support of the biobank construction (tissue preparation and tissue microarray construction).
Research activities
The followings are the major research highlights of this year.
1) A large amount of type I collagen is known to exist around cancer tissues. In this study, we found that the uptake of type I collagen by macropinocytosis causes mTOR activation, which leads to resistance to molecular targeted drugs and anticancer agents.
2) Using a novel in vitro invasion model we developed, we showed that certain biological features of cancer stem cells (e.g., enhanced invasiveness) are only apparent in the microenvironment where fibroblasts are present.
3) Using the results of exome analysis of lung adenocarcinoma specimens, we found that mutational smoking signature positive cases had a suppressive cancer immune microenvironment (high number of infiltrating FOXP3+ lymphocytes).
4) We created digital images of squamous cell carcinoma of the lungs and quantified the proportion of tumor cells, stromal cells, and necrotic cells by using a machine learning method. The results showed that a higher percentage of stromal component was a poor prognostic factor.
Education
We provide research guidance and education to the residents of the East Hospital. We also provide special lectures to residents who belong to the doctoral programs of Juntendo University Graduate School, which are affiliated with the National Cancer Center. Some of the staff also serve as adjunct faculty at the Graduate School of Frontier Sciences, University of Tokyo, where they provide research guidance and education for one doctoral student and four masters students.
Future Prospects
1) Our aim is to develop new diagnostic/therapeutic methods and search for biomarkers with clinicians and companies using abundant and quality-controlled histopathological specimens and detailed clinical information.
2) We will generate novel in vitro models that reproduce the human tumor microenvironment in vivo. For this purpose, we will focus on cell isolation from quality-controlled human cancer tissues, especially isolation and the culture of cancer associated fibroblasts (CAFs), and creating a CAF bank in the future.
List of papers published in 2020
Journal
1. Shiraishi T, Ikeda K, Tsukada Y, Nishizawa Y, Sasaki T, Ito M, Kojima M, Ishii G, Tsumura R, Saijou S, Koga Y, Yasunaga M, Matsumura Y. High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer. BMC Cancer, 21:302, 2021
2. Katsumata S, Aokage K, Ishii G, Hoshino H, Suzuki J, Miyoshi T, Tane K, Samejima J, Tsuboi M. Pathological features and prognostic implications of ground-glass opacity components on computed tomography for clinical stage I lung adenocarcinoma. Surg Today, 51:1188-1202, 2021
3. Morisue R, Kojima M, Suzuki T, Nakatsura T, Ojima H, Watanabe R, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Ishii G, Gotohda N, Fujiwara T, Ochiai A. Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses. Int J Cancer, 149:546-560, 2021
4. Amemiya R, Miyoshi T, Aokage K, Suzuki J, Hoshino H, Udagawa H, Tane K, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Goto K, Ikeda N, Tsuboi M, Ishii G. Prognostic impact of the tumor immune microenvironment in pulmonary pleomorphic carcinoma. Lung Cancer, 153:56-65, 2021
5. Sekihara K, Aokage K, Hiyama T, Oiwa H, Miyoshi T, Tane K, Ishii G, Tsuboi M. Prognostic impact of home oxygen therapy on patients with resected non-small-cell lung cancer with interstitial lung disease. Surg Today, 51:1036-1043, 2021
6. Suzuki J, Aokage K, Neri S, Sakai T, Hashimoto H, Su Y, Yamazaki S, Nakamura H, Tane K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Tsuboi M, Ishii G. Relationship between podoplanin-expressing cancer-associated fibroblasts and the immune microenvironment of early lung squamous cell carcinoma. Lung Cancer, 153:1-10, 2021
7. Su Y, Yamazaki S, Morisue R, Suzuki J, Yoshikawa T, Nakatsura T, Tsuboi M, Ochiai A, Ishii G. Tumor-Infiltrating T Cells Concurrently Overexpress CD200R with Immune Checkpoints PD-1, CTLA-4, and TIM-3 in Non-Small-Cell Lung Cancer. Pathobiology, 88:218-227, 2021
8. Mpekris F, Panagi M, Voutouri C, Martin JD, Samuel R, Takahashi S, Gotohda N, Suzuki T, Papageorgis P, Demetriou P, Pierides C, Koumas L, Costeas P, Kojima M, Ishii G, Constantinidou A, Kataoka K, Cabral H, Stylianopoulos T. Normalizing the Microenvironment Overcomes Vessel Compression and Resistance to Nano-immunotherapy in Breast Cancer Lung Metastasis. Adv Sci (Weinh), 8:2001917, 2021
9. Sakai T, Udagawa H, Matsumoto S, Yoh K, Nosaki K, Ikeda T, Zenke Y, Kirita K, Niho S, Akimoto T, Goto K, Ishii G. Morphological, immune and genetic features in biopsy sample associated with the efficacy of pembrolizumab in patients with non-squamous non-small cell lung cancer. J Cancer Res Clin Oncol, 147:1227-1237, 2021
10. Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol, 38:4292-4301, 2020
11. Kumagai S, Togashi Y, Kamada T, Sugiyama E, Nishinakamura H, Takeuchi Y, Vitaly K, Itahashi K, Maeda Y, Matsui S, Shibahara T, Yamashita Y, Irie T, Tsuge A, Fukuoka S, Kawazoe A, Udagawa H, Kirita K, Aokage K, Ishii G, Kuwata T, Nakama K, Kawazu M, Ueno T, Yamazaki N, Goto K, Tsuboi M, Mano H, Doi T, Shitara K, Nishikawa H. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol, 21:1346-1358, 2020
12. Kubota Y, Kawazoe A, Sasaki A, Mishima S, Sawada K, Nakamura Y, Kotani D, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Ishii G, Kuwata T, Shitara K. The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer. Clin Cancer Res, 26:3784-3790, 2020
13. Ishii T, Kawazoe A, Sasaki A, Mishima S, Kentaro S, Nakamura Y, Kotani D, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Kuwata T, Ishii G, Shitara K. Clinical and molecular factors for selection of nivolumab or irinotecan as third-line treatment for advanced gastric cancer. Ther Adv Med Oncol, 12:1758835920942377, 2020
14. Udagawa H, Kirita K, Naito T, Nomura S, Ishibashi M, Matsuzawa R, Hisakane K, Usui Y, Matsumoto S, Yoh K, Niho S, Ishii G, Goto K. Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single-arm study. Cancer Sci, 111:2488-2498, 2020
15. Ishii G, Ishii T. Review of cancer-associated fibroblasts and their microenvironment in post-chemotherapy recurrence. Hum Cell, 33:938-945, 2020
16. Koike Y, Aokage K, Ikeda K, Nakai T, Tane K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Tanaka T, Suzuki K, Tsuboi M, Ishii G. Machine learning-based histological classification that predicts recurrence of peripheral lung squamous cell carcinoma. Lung Cancer, 147:252-258, 2020
17. Sato K, Mimaki S, Yamashita R, Togashi Y, Naito T, Udagawa H, Katsumata S, Nakasone S, Miyoshi T, Tane K, Aokage K, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Goto K, Tsuboi M, Tsuchihara K, Ishii G. Association between the mutational smoking signature and the immune microenvironment in lung adenocarcinoma. Lung Cancer, 147:12-20, 2020
18. Inaba A, Hori K, Yoda Y, Ikematsu H, Takano H, Matsuzaki H, Watanabe Y, Takeshita N, Tomioka T, Ishii G, Fujii S, Hayashi R, Yano T. Artificial intelligence system for detecting superficial laryngopharyngeal cancer with high efficiency of deep learning. Head Neck, 42:2581-2592, 2020
19. Kudo M, Kobayashi T, Gotohda N, Konishi M, Takahashi S, Kobayashi S, Sugimoto M, Okubo S, Martin J, Cabral H, Ishii G, Kojima M. Clinical Utility of Histological and Radiological Evaluations of Tumor Necrosis for Predicting Prognosis in Pancreatic Cancer. Pancreas, 49:634-641, 2020
20. Yamazaki S, Su Y, Maruyama A, Makinoshima H, Suzuki J, Tsuboi M, Goto K, Ochiai A, Ishii G. Uptake of collagen type I via macropinocytosis cause mTOR activation and anti-cancer drug resistance. Biochem Biophys Res Commun, 526:191-198, 2020
21. Sekihara K, Aokage K, Miyoshi T, Tane K, Ishii G, Tsuboi M. Perioperative pirfenidone treatment as prophylaxis against acute exacerbation of idiopathic pulmonary fibrosis: a single-center analysis. Surg Today, 50:905-911, 2020
22. Oki T, Aokage K, Nomura S, Tane K, Miyoshi T, Shiiya N, Funai K, Tsuboi M, Ishii G. Optimal method for measuring invasive size that predicts survival in invasive mucinous adenocarcinoma of the lung. J Cancer Res Clin Oncol, 146:1291-1298, 2020
23. Miyashita T, Neri S, Hashimoto H, Akutsu A, Sugano M, Fujii S, Ochiai A, Ishii G. Fibroblasts-dependent invasion of podoplanin-positive cancer stem cells in squamous cell carcinoma. J Cell Physiol, 235:7251-7260, 2020