Review
Immunology
Raefa Abou Khouzam, Klaudia Brodaczewska, Aleksandra Filipiak, Nagwa Ahmed Zeinelabdin, Stephanie Buart, Cezary Szczylik, Claudine Kieda, Salem Chouaib
Summary: The environmental and metabolic pressures in the tumor microenvironment have a significant impact on tumor development, especially hypoxia-triggered events that promote growth, enhance resistance to the immune response, and stimulate angiogenesis. Normalizing tumor vasculature can restore integrity, increase perfusion, alleviate hypoxia, and reshape anti-tumor immunity, offering potential in achieving stable vascular normalization for mature and functional blood vessels.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ken Liu, Jinbiao Chen, Yang Zhao, Jade Boland, Ka Ka Ting, Glen Lockwood, Catriona McKenzie, James Kench, Mathew A. Vadas, Jennifer R. Gamble, Geoffrey W. McCaughan
Summary: Liver cancers have abnormal vasculature, hypoxia, and immunosuppressive microenvironment. Normalization of tumor vasculature and combination of immune checkpoint inhibition have been effective in treating liver cancer. This study demonstrated that CD5-2 combined with checkpoint inhibition effectively reduced liver tumor size and improved immune infiltrate.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Areez Shafqat, Mohamed H. Omer, Eman Nayaz Ahmed, Ali Mushtaq, Eman Ijaz, Zara Ahmed, Khaled Alkattan, Ahmed Yaqinuddin
Summary: This review focuses on the immunosuppressive effects of tumor angiogenesis and coagulation on the tumor microenvironment (TME). We summarize previous research efforts leveraging these observations and targeting these processes to enhance immunotherapy outcomes. Clinical trials have documented improved outcomes when combining anti-angiogenic agents and immunotherapy, but limitations and variable treatment outcomes have been noted. Understanding the key questions and directions for further research in this field is crucial for developing effective strategies to reprogram the TME in order to advance cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Ting Yu, Wen Nie, Zehua Hong, Yihong He, Jing Chen, Xue Mi, Shuping Yang, Xiaoling Li, Bilan Wang, Yunzhu Lin, Xiang Gao
Summary: By utilizing the RGD-DMA/pCCL19-BMS-1 system, significant inhibition of tumor progression was achieved, along with induction of locally high concentrations of immunostimulatory cytokines at tumor sites, effectively reshaping the immunosuppressive TME.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Immunology
Song Li, Pengxiang Chen, Bo Cheng, Yuchen Liu, Xue Zhang, Qian Xu, Miao Huang, Xin Dai, Kai Huang, Lin Zhang, Yufeng Cheng, Lian Liu
Summary: This study evaluated the impact of Pyroptosis potential in cancer patients and found that high potential is associated with tumor characteristics and response rates to immunotherapy. Pyroptosis scoring showed predictive value in immunotherapy outcomes. Additionally, systemic treatments can enhance Pyroptosis in drug-resistant tumors.
CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Felix Blanc-Durand, Catherine Genestie, Elisa Yaniz Galende, Sebastien Gouy, Philippe Morice, Patricia Pautier, Amandine Maulard, Soizick Mesnage, Audrey Le Formal, Chloe Brizais, Michael Richardson, Alexandra Leary
Summary: This study investigated the expression of immune co-regulators in epithelial ovarian cancer (EOC) and found that TIM3 was the most prevalent co-regulator. Most ovarian tumors expressed 2 or more co-inhibitory molecules, but these biomarkers were not correlated with each other. Neoadjuvant chemotherapy significantly impacted the expression of immune co-regulators, and there was no significant difference in the pattern of co-regulator expression between platinum-sensitive and resistant patients.
GYNECOLOGIC ONCOLOGY
(2021)
Review
Immunology
Jingyao Tu, Hang Liang, Chunya Li, Yongbiao Huang, Ziqi Wang, Xinyi Chen, Xianglin Yuan
Summary: Tumor immunotherapy has become a focus of research and treatment due to its effectiveness and fewer side effects compared to traditional treatments. However, the abnormal angiogenesis state of tumors can affect the efficacy of immunotherapy. The application of anti-angiogenesis drugs to normalize tumor vessels has shown promise in improving the effectiveness of immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Mario Rosario D'Andrea, Vittore Cereda, Luigi Coppola, Guido Giordano, Andrea Remo, Elena De Santis
Summary: Neoangiogenesis and various components of the tumor microenvironment are crucial in early metastatic spreading of breast cancer. Understanding the characteristics of the breast tumor environment, especially in correlation with hormone receptors and HER2 status, is important for diagnostic algorithms. The tumor microenvironment, including immune and non-immune cells, as well as cytokines, plays a critical role in breast cancer biology, impacting prognosis and treatment response.
Article
Chemistry, Multidisciplinary
Ruoyu Shen, Lijun Peng, Wentao Zhou, Ding Wang, Qi Jiang, Jian Ji, Fuqiang Hu, Hong Yuan
Summary: Abnormal tumor vasculature leads to malignant tumor microenvironment and affects tumor progression. We developed a nano-delivery system that sustains the release of anti-angiogenic agents to stabilize tumor vascular normalization, improving tumor perfusion and reversing abnormalities in the tumor microenvironment, ultimately inhibiting tumor progression.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Biochemistry & Molecular Biology
Kamila Wojas-Krawczyk, Iwona Pasnik, Tomasz Kucharczyk, Irena Wieleba, Natalia Krzyzanowska, Michal Gil, Pawel Krawczyk, Janusz Milanowski
Summary: Immunotherapy's predictive factors are limited, requiring consideration of multiple factors. Specific stimulation of lymphocytes and recognition of tumor antigens are crucial. Multi-parameter immune system analysis is considered a future-oriented predictive marker.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Chengheng Liao, Xijuan Liu, Cheng Zhang, Qing Zhang
Summary: Hypoxia, characterized by diminished oxygen availability, has a significant impact on the tumor microenvironment, leading to abnormal vasculature, altered metabolism, and immune suppression. Limited effectiveness and development of resistance to anti-tumor therapy are also associated with hypoxia in the tumor microenvironment. This review summarizes the molecular mechanisms underlying hypoxic cellular responses and adaptations, and emphasizes the effects of hypoxia on angiogenesis, cellular metabolism, and immune suppression within the tumor microenvironment. Additionally, the recent advances in targeting hypoxia for therapeutic implications are discussed. A comprehensive understanding of hypoxia and its role in tumors will contribute to the development of improved cancer treatments.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Min Hu, Yongfu Li, Yuting Lu, Miao Wang, Yingrui Li, Chaoying Wang, Qin Li, Hong Zhao
Summary: Hypoxia in the tumor microenvironment influences the expression of immune checkpoints, interfering with the anti-tumor response of immune effector cells and facilitating immune evasion by tumors. Combination therapy with HIF-1α inhibitors, Ado inhibitors, and ICIs shows promising efficacy, suggesting that future combination therapy with hypoxia pathway inhibitors and ICIs may be an effective anti-tumor treatment strategy.
Article
Immunology
Xiaohan Zhou, Jun Du, Chengdong Liu, Hanyi Zeng, Yuting Chen, Li Liu, Dehua Wu
Summary: CD161 is a potential cancer biomarker that shows differential expression and better survival prediction in most tumor types. It is closely correlated with immunoregulatory interactions between lymphoid and non-lymphoid cells, as well as with T cell infiltration, immune checkpoints, immune activating genes, immunosuppressive genes, chemokines, and chemokine receptors. These findings suggest that CD161 may synergize with other immune checkpoints to regulate the immune microenvironment, making it a potential target for new immunotherapy drugs development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yuanji Feng, Jiayan Wu, Jie Chen, Lin Lin, Sijia Zhang, Zhiyu Yang, Pingjie Sun, Yanhui Li, Huayu Tian, Xuesi Chen
Summary: This study developed a revolutionary dual gene delivery system loading pshVEGF-A and pshPD-L1 to overcome adaptive resistance to ICB therapy, achieving effective anti-tumor immunotherapy. The strategy eliminates adaptive resistance, achieves tumor vessel normalization, and reprograms the tumor immune microenvironment, contributing to the diversity of immune combination therapy.
Article
Multidisciplinary Sciences
Naidong Zhang, Rongping Yin, Pei Zhou, Xiaomei Liu, Peng Fan, Long Qian, Li Dong, Chenglin Zhang, Xichen Zheng, Shengming Deng, Jiajie Kuai, Zhenhua Liu, Wen Jiang, Xiaohua Wang, Depei Wu, Yuhui Huang
Summary: Elevated levels of DLL1 in the TME promote long-term tumor vascular normalization, accumulation of CD8+ T cells, M1-like macrophage polarization, and increase the sensitivity of anti-CTLA4 therapy in resistant tumors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Natasha Ustyanovska Avtenyuk, Ghizlane Choukrani, Emanuele Ammatuna, Toshiro Niki, Ewa Cendrowicz, Harm Jan Lourens, Gerwin Huls, Valerie R. Wiersma, Edwin Bremer
Summary: In this study, Gal-9 treatment was found to induce significant membrane alterations in cancer cells by externalizing phosphatidyl serine (PS) and downregulating the anti-phagocytic regulator CD47. It was also shown to trigger trogocytosis and enhance antibody-dependent cellular phagocytosis of cancer cells by activating neutrophils and mobilizing granules. Moreover, Gal-9 treatment resulted in decreased cancer cell adhesion and potent cytotoxicity mediated by neutrophils.
Article
Oncology
Ewa Cendrowicz, Lisa Jacob, Shirley Greenwald, Ami Tamir, Iris Pecker, Rinat Tabakman, Lucy Ghantous, Liat Tamir, Roy Kahn, Jasmine Avichzer, Alexandra Aronin, Shira Amsili, Elina Zorde-Khvalevsky, Yosi Gozlan, Martijn Vlaming, Gerwin Huls, Tom van Meerten, Michal Elhalel Dranitzki, Adam Foley-Comer, Yaron Pereg, Amnon Peled, Ayelet Chajut, Edwin Bremer
Summary: DSP107 effectively (re)activates innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Joyce M. Lubbers, Marta A. Wazynska, Nienke van Rooij, Arjan Kol, Hagma H. Workel, Annechien Plat, Sterre T. Paijens, Martijn R. Vlaming, Diana C. J. Spierings, Philip H. Elsinga, Edwin Bremer, Hans W. Nijman, Marco de Bruyn
Summary: Identification of CD8+ T cells that react to human cancer is important for immunotherapy stratification and assessment of immune-therapeutic effects. In this study, a subset of CD103- CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors were found to be predominantly characterized by expression of TNFRSF9. These cells were recently activated and likely rapidly differentiated towards tissue residence upon exposure to TGF-beta in the tumor micro-environment, explaining their relative paucity in human tumors.
Article
Biochemistry & Molecular Biology
Jimena Alvarez Freile, Natasha Ustyanovska Avtenyuk, Macarena Gonzalez Corrales, Harm Jan Lourens, Gerwin Huls, Tom van Meerten, Ewa Cendrowicz, Edwin Bremer
Summary: This study investigates the expression and therapeutic effects of CD24 and CD47, two immune checkpoints, in B-cell lymphoma. The results show that CD24 is associated with poor survival in MCL patients, while CD47 is associated with survival in DLBCL patients. CD24 antibody treatment exhibits potent phagocytic effects in MCL, but not in DLBCL.
Article
Oncology
Vrouyr Bilemjian, Martijn R. Vlaming, Jimena Alvarez Freile, Gerwin Huls, Marco De Bruyn, Edwin Bremer
Summary: This article investigates the role of the GPR56 immune checkpoint in tumor infiltrating lymphocytes in epithelial ovarian cancer. The expression of GPR56 differs between cancer and healthy cells, and ectopic expression of GPR56 reduces T cell migration.
Review
Oncology
Renee Bouwstra, Tom van Meerten, Edwin Bremer
Summary: The CD47-SIRP alpha 'don't eat me' signaling axis is a prominent innate immune checkpoint, but monotherapy has limited therapeutic effect and severe side effects. Promising clinical responses have been seen with combination therapy, but toxicity issues remain. Innovations include novel antibody formats targeting CD47 on tumor cells and tumor-targeted bispecific antibodies. Combinatorial approaches with opsonizing antibodies, systemic therapy, epigenetic drugs, T-cell-targeted therapeutics, or dual immunomodulatory CD47 bispecific antibodies aim to improve the therapeutic effect of CD47 blockade.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Martijn Vlaming, Vrouyr Bilemjian, Jimena Alvarez Freile, Vinicio Melo, Annechien Plat, Gerwin Huls, Hans W. Nijman, Marco de Bruyn, Edwin Bremer
Summary: Reactivation of tissue-resident memory T cells expressing TIM-3 and CXCL13 in epithelial ovarian cancer is associated with improved patient survival, suggesting a potential therapeutic target for anti-cancer immunotherapy in EOC patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Lucy Ghantous, Yael Volman, Ruth Hefez, Ori Wald, Esther Stern, Tomer Friehmann, Ayelet Chajut, Edwin Bremer, Michal Dranitzki Elhalel, Jacob Rachmilewitz
Summary: CD47 is upregulated following DNA damage, including irradiation, which depends on the key factor Mre11 in the DNA damage response pathway. CD47 is a cell surface ligand expressed on all nucleated cells and acts as an immune checkpoint protein to prevent phagocytosis. It is constitutively overexpressed in many tumors, but the underlying mechanism(s) for CD47 overexpression is unclear.
COMMUNICATIONS BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Kai Li, Yusheng Lin, Yu Zhou, Xiao Xiong, Lu Wang, Junkuo Li, Fuyou Zhou, Yi Guo, Shaobin Chen, Yuping Chen, Hui Tang, Xiaofu Qiu, Songwang Cai, Dianzheng Zhang, Edwin Bremer, Sai-Ching Jim Yeung, Hao Zhang
Summary: This study aims to establish a biomarker for early detection and risk stratification of esophageal squamous cell carcinoma (ESCC) using microRNA (miRNA) derived from salivary extracellular vesicles and particles (EVPs). The study identifies a 6-miRNA signature that accurately distinguishes patients with early-stage ESCC from control subjects, and successfully validates its effectiveness.
Article
Immunology
Jimena Alvarez Freile, Yuzhu Qi, Lisa Jacob, Maria Franceskin Lobo, Harm Jan Lourens, Gerwin Huls, Edwin Bremer
Summary: Investigations into the strength of antigen-specific responses in vitro are crucial for early-phase research of immunotherapeutic approaches. This study presents a rapid luminescence-based method using HPV16 E7(11-20) peptide as a model antigen to evaluate MHC-dependent antigen-specific T cell responses in vitro. The method has important implications for assessing the impact of tumor microenvironment and immune checkpoint inhibitors, as well as accelerating the development of novel immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Vinicio Melo, Levi Collin Nelemans, Martijn Vlaming, Harm Jan Lourens, Valerie R. Wiersma, Vrouyr Bilemjian, Gerwin Huls, Marco de Bruyn, Edwin Bremer
Summary: A bispecific antibody, CD27xEGFR, has been developed to re-activate T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27. CD27xEGFR binds to both CD27 and EGFR simultaneously, triggering EGFR-restricted co-stimulation of T cells and enhancing T cell cytotoxicity against cancer cells. It has the potential to improve clinical outcomes in various cancers by overcoming the inhibitory factors that suppress T cell activity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Yuzhu Qi, Meifang Li, Shaozhong Li, De Zeng, Yingsheng Xiao, Jiwei Li, Qianqian Ye, Edwin Bremer, Guo-jun Zhang
Summary: This study explored the molecular mechanisms of chemoresistance in triple-negative breast cancer (TNBC) and found that Notch1 and CD73 were associated with poor clinical outcome in cisplatin-treated patients. Further experiments revealed that Notch1 regulated CD73 expression by directly binding to the CD73 promoter. These findings suggest that CD73 is a direct downstream target of Notch1 in mediating cisplatin resistance in TNBC.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Ghizlane Choukrani, Nienke Visser, Natasha Ustyanovska Avtenyuk, Mirjam Olthuis, Glenn Marsman, Emanuele Ammatuna, Harm Jan Lourens, Toshiro Niki, Gerwin Huls, Edwin Bremer, Valerie R. Wiersma
Summary: AML is a malignancy associated with poor survival rates, especially due to therapy-resistant relapse. The glycan-binding protein Gal-9 has shown tumor-selective cytotoxicity, dependent on autophagy inhibition, making it a potential therapeutic option for AML. In this study, Gal-9 was found to be cytotoxic for AML cells, including stem cells, and showed efficacy in AraC-resistant AML cases. It also enhanced the cytotoxic effect of Azacytidine, providing a possible treatment approach for AML patients not eligible for intensive AraC treatment.
CELL DEATH DISCOVERY
(2023)