Review
Biochemistry & Molecular Biology
Hui Wang, Tian Tian, Jinhua Zhang
Summary: Colorectal cancer (CRC) is a highly prevalent and lethal malignant tumor in the digestive system. Tumor-associated macrophages (TAMs) play a crucial role in various mechanisms of CRC progression, such as promoting tumor proliferation, invasion, angiogenesis, and immunosuppression, although their exact role is still debated in clinical evidence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Hao Wang, Jinwen Yin, Yuntian Hong, Anli Ren, Haizhou Wang, Mengting Li, Qiu Zhao, Congqing Jiang, Lan Liu
Summary: In this study, the researchers found that SCG2 expression was significantly decreased in CRC tumor tissues and differentially distributed between tumor and adjacent normal tissues. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate tumor immunity by influencing immune cell infiltration and macrophage polarization in CRC.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Sara A. Vayrynen, Jinming Zhang, Chen Yuan, Juha P. Vayrynen, Andressa Dias Costa, Hannah Williams, Vicente Morales-Oyarvide, Mai Chan Lau, Douglas A. Rubinson, Richard F. Dunne, Margaret M. Kozak, Wenjia Wang, Diana Agostini-Vulaj, Michael G. Drage, Lauren Brais, Emma Reilly, Osama Rahma, Thomas Clancy, Jiping Wang, David C. Linehan, Andrew J. Aguirre, Charles S. Fuchs, Lisa M. Coussens, Daniel T. Chang, Albert C. Koong, Aram F. Hezel, Shuji Ogino, Jonathan A. Nowak, Brian M. Wolpin
Summary: The study revealed a diverse set of myeloid cells within the PDAC tumor microenvironment, which are distributed heterogeneously across patient tumors. Beyond cell density, the spatial locations of immune cells are also associated with patient outcomes, underscoring the potential role of spatially resolved myeloid cell subtypes as quantitative biomarkers for PDAC prognosis and therapy.
CLINICAL CANCER RESEARCH
(2021)
Review
Immunology
Maorun Zhang, Xiaoping Li, Qi Zhang, Jiahua Yang, Gang Liu
Summary: Colitis-associated colorectal cancer (CAC) is a severe complication of ulcerative colitis (UC), characterized by multiple lesions, worse pathological type, and poor prognosis. Macrophages, as innate immune cells, play a crucial role in both inflammatory response and tumor immunity. Enhanced macrophage infiltration in UC leads to the production of inflammatory cytokines, promoting UC tumorigenesis. Macrophage polarization into M1 has an anti-tumor effect, while M2 polarization promotes tumor growth. Targeting macrophages has shown effectiveness in preventing and treating CAC.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Chen Li, Jiagui Song, Zhengyang Guo, Yueqing Gong, Tengrui Zhang, Jiaqi Huang, Rui Cheng, Xiaotong Yu, Yanfang Li, Li Chen, Xiaojuan Ma, Yan Sun, Yan Wang, Lixiang Xue
Summary: This study investigates the role of EZH2 inhibitors in modulating macrophage polarization in the tumor microenvironment of colorectal cancer. The two different EZH2 inhibitors, EPZ6438 and GSK126, were compared. The findings suggest that EZH2 inhibitors not only suppress CRC cell proliferation directly, but also regulate macrophage polarization to exert a tumor suppressive effect.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Angela DeRosa, Avigdor Leftin
Summary: Macrophages play important roles in systemic iron metabolism and immune response. Infiltration and polarization of macrophages in the tumor microenvironment are associated with cancer prognosis, with distinct iron and immune phenotypes observed in tumor associated macrophages in most cancers. Functional connections between dysfunctional iron metabolism and tumor immune response are emerging, providing new insights for immunometabolic precision therapy approaches.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, Research & Experimental
Alireza Najafi, Maryam Keykhaee, Hossein Khorramdelazad, Mohammad Yahya Karimi, Leila Nejatbakhsh Samimi, Nazanin Aghamohamadi, Milad Karimi, Reza Falak, Mehdi Khoobi
Summary: The tumor microenvironment (TME) plays a critical role in tumor progression and resistance to treatment. Tumor-associated macrophages (TAMs) and hypoxia are important factors in the TME. Catalase and catalase-mimicking compounds can reduce hypoxia and promote TAM polarization, showing potential in cancer therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Oncology
Cong Li, Shi Qiu, Kun Jin, Xiaonan Zheng, Xianghong Zhou, Di Jin, Binghe Xu, Xun Jin
Summary: The study revealed that tumor cells in triple-negative breast cancer can release microparticles loaded with PD-L1, leading to tumor progression. These PD-L1-loaded microparticles can suppress the activation and function of immune cells through various mechanisms.
Review
Immunology
Tingting Xia, Meng Zhang, Wei Lei, Ruilin Yang, Shengping Fu, Zhenhai Fan, Ying Yang, Tao Zhang
Summary: Cell growth, proliferation, differentiation, and apoptosis are influenced by STAT3, and aberrant STAT3 expression affects the development of inflammatory immunological disorders, fibrotic diseases, and malignancies. Macrophages (M0) can be polarized into pro-inflammatory (M1) and anti-inflammatory (M2) types, and STAT3 signaling plays a role in this polarization. This review compiles the relevant signaling pathways associated with STAT3 and macrophage polarization for the treatment and investigation of disorders related to macrophage polarization.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Adriana Grigoras, Cornelia Amalinei
Summary: Colorectal cancer (CRC) is a common type of cancer, particularly in obese patients, and is a leading cause of cancer-related death. Cancer-associated adipocytes (CAAs) play a crucial role in the tumor microenvironment (TME) of CRC, aiding in cancer cell development through the release of metabolites, growth factors, and inflammatory adipokines. CAAs also affect the immune response, metabolic reprogramming, and chemotherapeutic resistance in colon cancer cells.
Article
Biochemistry & Molecular Biology
Lin Gan, Changjiang Yang, Long Zhao, Shan Wang, Zhidong Gao, Yingjiang Ye
Summary: The study investigated the expression level and function of SPOCD1 in colorectal cancer (CRC) by analyzing large-scale databases and clinical samples. The results showed that elevated SPOCD1 expression was associated with poor prognosis in CRC, and it could act as an oncogene by regulating gene expression in crucial functions and pathways of tumorigenesis. Moreover, SPOCD1 was also associated with immune cells, especially macrophages, suggesting a possible role in macrophage polarization in CRC.
Review
Immunology
Yaping Chen, Xiao Zheng, Changping Wu
Summary: Colorectal cancer has the second highest mortality rate globally, and various treatments have improved patient survival. The emergence of ICIs as a new immunotherapy option for advanced CRC is promising, highlighting the importance of understanding the relationship between tumor immune microenvironment and immunotherapy efficacy for selecting appropriate treatment strategies. This review outlines the latest research progress in the immune microenvironment and immunotherapy strategies for CRC.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Shirin Tavana, Zahra Mokhtari, Mohammad Hossein Sanei, Zahra Heidari, Amir-Reza Dehghanian, Zahra Faghih, Marzieh Rezaei
Summary: This study investigated the presence of CD45RO+, LAG3+, CD3+, and CD8+ lymphocytes in colorectal cancer (CRC) tumor tissues and their association with clinicopathological parameters and patient survival. The results showed that CD45RO+ and CD3+ cells were the most frequent infiltrating lymphocytes in colon tumor tissues, while LAG3+ lymphocytes were the least frequent subset. The frequency of CD45RO+ TILs was positively associated with advanced TNM stages, and high scores of CD45RO+ TILs in the invasive margin were associated with better overall survival.
CANCER CELL INTERNATIONAL
(2023)
Review
Biochemistry & Molecular Biology
Huogang Wang, Mingo M. H. Yung, Hextan Y. S. Ngan, Karen K. L. Chan, David W. Chan
Summary: Metastasis, driven by tumor-associated macrophages (TAMs), is a key factor in most cancer deaths, with TAMs playing a crucial role in influencing tumor metastasis and treatment outcomes by polarizing metabolism patterns. Tumor cell-driven TAMs in the tumor microenvironment promote tumor metastasis and are associated with poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Srijan Dubey, Sayak Ghosh, Debosmita Goswami, Debapriya Ghatak, Rudranil De
Summary: Macrophages are immune cells that can engulf and destroy target cells, including tumor cells. Some macrophages undergo a change to become polarized M2 macrophages while devouring cancer cells. M2 macrophages play important roles in metastasis, tumor suppression, and angiogenesis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Surgery
Tomohiko Taniai, Koichiro Haruki, Mitsuru Yanagaki, Yosuke Igarashi, Kenei Furukawa, Shinji Onda, Jungo Yasuda, Michinori Matsumoto, Masashi Tsunematsu, Toru Ikegami
Summary: This study aimed to evaluate the prognostic significance of osteosarcopenia in patients with intrahepatic cholangiocarcinoma (IHCC). The results showed that osteosarcopenia was associated with disease-free and overall survival, and it may serve as a predictor of adverse prognosis for patients undergoing hepatic resection for IHCC.
Article
Oncology
Koichiro Haruki, Tomohiko Taniai, Mitsuru Yanagaki, Kenei Furukawa, Masashi Tsunematsu, Shinji Onda, Yoshihiro Shirai, Michinori Matsumoto, Norimitsu Okui, Toru Ikegami
Summary: This study found that sustained elevated CAR after resection may be an important indicator for predicting long-term outcomes in patients with hepatocellular carcinoma, suggesting a relationship between the host's inflammatory state and tumor recurrence and progression.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Koichiro Haruki, Tomohiko Taniai, Mitsuru Yanagaki, Kenei Furukawa, Masashi Tsunematsu, Shinji Onda, Yoshihiro Shirai, Michinori Matsumoto, Norimitsu Okui, Toru Ikegami
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Koichiro Haruki, Tomohiko Taniai, Mitsuru Yanagaki, Kenei Furukawa, Masashi Tsunematsu, Shinji Onda, Yoshihiro Shirai, Michinori Matsumoto, Norimitsu Okui, Toru Ikegami
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Hannah L. Williams, Andressa Dias Costa, Jinming Zhang, Srivatsan Raghavan, Peter S. Winter, Kevin S. Kapner, Scott P. Ginebaugh, Sara A. Vayrynen, Juha P. Vayrynen, Chen Yuan, Andrew W. Navia, Junning Wang, Annan Yang, Timothy L. Bosse, Radha L. Kalekar, Kristen E. Lowder, Mai Chan Lau, Dalia Elganainy, Vicente Morales-Oyarvide, Douglas A. Rubinson, Harshabad Singh, Kimberly Perez, James M. Cleary, Thomas E. Clancy, Jiping Wang, Joseph D. Mancias, Lauren K. Brais, Emma R. Hill, Margaret M. Kozak, David C. Linehan, Richard F. Dunne, Daniel T. Chang, Albert C. Koong, Aram F. Hezel, William C. Hahn, Alex K. Shalek, Andrew J. Aguirre, Jonathan A. Nowak, Brian M. Wolpin
Summary: A multiplex immunofluorescence (mIF) pipeline was developed to investigate the protein expression and intratumoral heterogeneity of pancreatic ductal adenocarcinoma (PDAC). The results showed that PDAC tumors exhibit extensive intratumoral heterogeneity, which is associated with patient outcomes and can be reduced in patient-derived organoid cultures. Co-expressor cells expressing both classical and basal markers were found in the majority of tumors, suggesting an intermediate state between subtype poles. This clinically applicable pipeline has implications for prognosis and treatment selection in PDAC patients.
Article
Surgery
Yasuhiro Takano, Koichiro Haruki, Wataru Kai, Shu Tsukihara, Yasunobu Kobayashi, Daisuke Ito, Hironori Kanno, Kyonsu Son, Nobuyoshi Hanyu, Ken Eto
Summary: This study found a relationship between preoperative serum cholinesterase levels and postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia.
Article
Gastroenterology & Hepatology
Masashi Tsunematsu, Koichiro Haruki, Tomohiko Taniai, Yoshiaki Tanji, Yoshihiro Shirai, Kenei Furukawa, Tadashi Uwagawa, Shinji Onda, Mitsuru Yanagaki, Teruyuki Usuba, Yukio Nakabayashi, Tomoyoshi Okamoto, Toru Ikegami
Summary: The aim of this study was to investigate the prognostic value of the CALLY index (C-reactive protein-albumin-lymphocyte index) in patients with distal cholangiocarcinoma after pancreaticoduodenectomy. The results showed that the CALLY index was associated with disease-free survival and overall survival, suggesting its importance as an indicator for long-term outcomes in these patients.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Multidisciplinary Sciences
Liisa Petainen, Juha P. Vayrynen, Pekka Ruusuvuori, Ilkka Polonen, Sami Ayramo, Teijo Kuopio
Summary: This study proposes an automated method for estimating tumor-stroma ratio (TSR) from histopathological images of colorectal cancer using convolutional neural networks. The models achieved high accuracy in classifying stroma, tumor, and other tissues, with the best model reaching 99.3% accuracy for tumor classification. The predicted TSR values showed moderate correlation with pathologist estimations (0.57).
Article
Pathology
Topias Karjula, Anne Niskakangas, Olli Mustonen, Iiris Puro, Hanna Elomaa, Maarit Ahtiainen, Teijo Kuopio, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Fredrik Yannopoulos, Olli Helminen, Juha P. Vayrynen
Summary: In this study, the prognostic effect of tertiary lymphoid structures (TLSs) on colorectal cancer (CRC) pulmonary metastases and primary tumors was analyzed. The density and diameter of TLSs showed no prognostic value in pulmonary metastases, but higher density and diameter were associated with lower mortality in primary tumors.
Article
Multidisciplinary Sciences
Pei-Chen Tsai, Tsung-Hua Lee, Kun-Chi Kuo, Fang-Yi Su, Tsung-Lu Michael Lee, Eliana Marostica, Tomotaka Ugai, Melissa Zhao, Mai Chan Lau, Juha P. Vayrynen, Marios Giannakis, Yasutoshi Takashima, Seyed Mousavi Kahaki, Kana Wu, Mingyang Song, Jeffrey A. Meyerhardt, Andrew T. Chan, Jung-Hsien Chiang, Jonathan Nowak, Shuji Ogino, Kun-Hsing Yu
Summary: The authors develop a machine learning-based platform, MOMA, to systematically identify and interpret the relationship between patients' histologic patterns, multi-omics, and clinical profiles. MOMA successfully predicts the overall survival, disease-free survival, and copy number alterations of colorectal cancer patients. Additionally, MOMA identifies interpretable pathology patterns predictive of gene expression profiles, microsatellite instability status, and clinically actionable genetic alterations.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jouni Harkonen, Petri Polonen, Ashik Jawahar Deen, Ilakya Selvarajan, Hanna-Riikka Teppo, Elitsa Y. Dimova, Thomas Kietzmann, Maarit Ahtiainen, Juha P. Vayrynen, Sara A. Vayrynen, Hanna Elomaa, Niko Tynkkynen, Tiia Eklund, Teijo Kuopio, Eva-Maria Talvitie, Pekka Taimen, Markku Kallajoki, Minna U. Kaikkonen, Merja Heinaniemi, Anna-Liisa Levonen
Summary: The NRF2 pathway is frequently activated in various cancer types, but a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and conducted a pan-cancer analysis of oncogenic NRF2 signaling using it. Our findings revealed an immunoevasive phenotype in squamous malignancies of the lung, head and neck area, cervix, and esophagus, where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression, and T cell and macrophage infiltration. These tumors have a molecular phenotype with amplification of SOX2/TP63, TP53 mutation, and CDKN2A loss, and are associated with upregulation of immunomodulatory genes NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1, and PD-L1. Our functional genomics analyses suggest that these genes are candidate NRF2 targets, indicating a direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands and increased expression of immunosuppressive ligands NAMPT, SPP1, and WNT5A involved in intercellular crosstalk. Moreover, the negative relationship between NRF2 and immune cells is explained by stromal populations of lung squamous cell carcinoma, indicating a potential effect across multiple squamous malignancies based on our molecular subtyping and deconvolution data.
Article
Gastroenterology & Hepatology
Keigo Nakashima, Koichiro Haruki, Teppei Kamada, Junji Takahashi, Yuichi Nakaseko, Hironori Ohdaira, Kenei Furukawa, Yutaka Suzuki, Toru Ikegami
Summary: This study analyzed the relationship between CXI and long-term outcomes of gastric cancer patients, and found that low CXI is an independent predictor of disease-free survival and overall survival for gastric cancer patients, suggesting the importance of comprehensive assessment of nutritional, physical, and inflammatory status in evaluating cachexia.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Surgery
Munetoshi Akaoka, Koichiro Haruki, Kenei Furukawa, Shinji Onda, Shunta Ishizaki, Masashi Tsunematsu, Yoshihiro Shirai, Norimitsu Okui, Yoshiaki Tanji, Toru Ikegami
Summary: This article reports a case of autologous portal Y-graft interposition after thrombectomy for a recipient with portal vein thrombosis in right lobe liver transplantation. The operation was successful and the patient recovered well postoperatively.
SURGICAL CASE REPORTS
(2023)
Article
Gastroenterology & Hepatology
Takashi Aida, Koichiro Haruki, Munetoshi Akaoka, Kenei Furukawa, Shinji Onda, Yoshihiro Shirai, Hironori Shiozaki, Keita Takahashi, Tsunekazu Oikawa, Toru Ikegami
Summary: This study investigated the prognostic value of the combined score of CAR and mALBI in predicting the prognosis of HCC patients after hepatic resection. The results showed that the CAR-mALBI score was associated with disease-free and overall survival in HCC patients, highlighting the importance of assessing hepatic functional reserve and host-inflammatory state in risk assessment.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Oncology
Kenei Furukawa, Koichiro Haruki, Tomohiko Taniai, Mitsuru Yanagaki, Masashi Tsunematsu, Yoshiaki Tanji, Shunta Ishizaki, Yoshihiro Shirai, Shinji Onda, Toru Ikegami
Summary: This study evaluated the prognostic significance of occult vertebral fracture (OVF) on the long-term outcomes of patients with colorectal liver metastases (CRLM) after hepatectomy and found that OVF is associated with prognosis. The results of this study have important implications for risk stratification and understanding clinical prognosis in these patients.