Article
Oncology
Sophia F. Magkouta, Photene C. Vaitsi, Marianthi P. Iliopoulou, Apostolos G. Pappas, Chrysavgi N. Kosti, Katherina Psarra, Ioannis T. Kalomenidis
Summary: The inhibition of MTH1 enhances immune cell function and improves the efficacy of immunotherapy, and combined use with PD-L1 can effectively treat mesothelioma.
Article
Oncology
Luca Cantini, Isaac Laniado, Vivek Murthy, Daniel Sterman, Joachim G. J. Aerts
Summary: Malignant pleural mesothelioma (MPM) is an aggressive tumor with low survival rates. Platinum-based chemotherapy has been the mainstay of treatment, but immunotherapy using immune check-point inhibitors (ICIs) has shown promise. However, the results from clinical trials using single ICIs have been conflicting, possibly due to the lack of specific biomarkers and patient heterogeneity. The study Checkmate743 demonstrated the superiority of a combination of ICIs over chemotherapy, leading to FDA approval for the treatment of unresectable MPM. This review discusses emerging immunotherapy strategies for MPM and highlights the importance of refining the approach in preclinical studies and strengthening collaboration in clinical trials.
Review
Biochemistry & Molecular Biology
Enrico Munari, Francesca R. Mariotti, Linda Quatrini, Pietro Bertoglio, Nicola Tumino, Paola Vacca, Albino Eccher, Francesco Ciompi, Matteo Brunelli, Guido Martignoni, Giuseppe Bogina, Lorenzo Moretta
Summary: Immune evasion is a crucial strategy adopted by tumor cells to promote survival and metastasis, with PD-1 playing a major role in inhibiting immune responses. Targeting the PD-1/PD-L1 axis has been a significant breakthrough in cancer treatment, representing unprecedented success in various cancer types. Further research on mechanisms regulating PD-1 expression and signaling in tumors is needed to improve therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Jie Mei, Yun Cai, Huiyu Wang, Rui Xu, Jiaofeng Zhou, Jiahui Lu, Xuejing Yang, Jiadong Pan, Chaoying Liu, Junying Xu, Yichao Zhu
Summary: This study aims to explore the expressions, prognostic values, and immunological correlations of Formins in cancer. DIAPH1 functioned as an oncogene in breast cancer and mediated epithelial-mesenchymal transformation (EMT) and PD-L1 expression. Moreover, DIAPH1 was overexpressed in most cancers and functioned as a novel pan-cancer immuno-marker, which could predict the response to anti-PD-1/PD-L1 immunotherapy.
CLINICAL IMMUNOLOGY
(2023)
Article
Oncology
Ivelina Spassova, Selma Ugurel, Linda Kubat, Lisa Zimmer, Patrick Terheyden, Annalena Mohr, Hannah Bjorn Andtback, Lisa Villabona, Ulrike Leiter, Thomas Eigentler, Carmen Loquai, Jessica C. Hassel, Thilo Gambichler, Sebastian Haferkamp, Peter Mohr, Claudia Pfoehler, Lucie Heinzerling, Ralf Gutzmer, Jochen S. Utikal, Kai Horny, Hans-Ulrich Schildhaus, Daniel Habermann, Daniel Hoffmann, Dirk Schadendorf, Juergen Christian Becker
Summary: This multicenter retrospective study of 114 unresectable MCC patients examined clinical and molecular characteristics to identify factors associated with a favorable response to PD-1/PD-L1 ICI therapy. Findings highlighted the absence of immunosuppression, limited number of tumor-involved organs, and a predominance of CD8(+) T-CM among TIL as key baseline parameters influencing therapy response in advanced MCC patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Chemistry, Multidisciplinary
Hamadi Madhi, Jeon-Soo Lee, Young Eun Choi, Yan Li, Myoung Hee Kim, Yongdoo Choi, Sung-Ho Goh
Summary: The focus of this study is FOXM1, which is identified as a potential therapeutic target for cancer immunotherapy and associated with the modulation of PD-L1 expression. The study found that selective knockdown of FOXM1 or treatment with TST significantly reduces PD-L1 expression in NSCLC cells and inhibits proliferation. Animal studies showed that TST treatment downregulates PD-L1 expression in NSCLC tumors and reduces tumor size without side effects. Combined treatment with TST and anti-4-1BB antibody induces synergistic therapeutic outcomes against immune resistant lung tumors and increases the number of CD3(+) T cells in tumor tissues.
Review
Immunology
Yusha Wang, Lei Zhang, Yun Bai, Li Wang, Xuelei Ma
Summary: Epithelial ovarian cancer is the second most common cause of gynecologic cancer death, and patients with advanced disease require more efficient treatment options. Immunotherapy seems to be a promising strategy, but the tumor microenvironment plays a crucial role in the response to immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Nian Liu, Mingjie Yan, Qian Tao, Jie Wu, Jing Chen, Xiang Chen, Cong Peng
Summary: The study identified significant metabolic alterations in glycolysis and the TCA cycle in melanoma patients and demonstrated the negative correlation between PDHA1, OGDH, and the efficacy of anti-PD-1 immunotherapy. Inhibiting PDHA1 and OGDH improved melanoma progression and therapeutic efficacy of anti-PD-1 treatment. Suppression of the TCA cycle led to increased PD-L1 expression and glycolysis flux, providing a potential novel strategy for melanoma treatment with anti-PD-1 immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Dominique Delmas, Francois Hermetet, Virginie Aires
Summary: Immunotherapies targeting PD-1/PD-L1 have shown promise in cancer treatment, but face challenges such as low response rates, high costs, and rare hyper-progression risks. The main focus is on improving existing therapies through combinatory approaches to overcome these limitations.
Article
Chemistry, Medicinal
Chengliang Sun, Mingxiao Yin, Yao Cheng, Zean Kuang, Xiaojia Liu, Gefei Wang, Xiao Wang, Kai Yuan, Wenjian Min, Jingwen Dong, Yi Hou, Lingrong Hu, Guoyu Zhang, Wenli Pei, Liping Wang, Yanze Sun, Xinmiao Yu, Yibei Xiao, Hongbin Deng, Peng Yang
Summary: S4-1 is an innovative small-molecule inhibitor of PD-L1 that effectively alters the PD-L1/PD-1 interaction, enhances cytotoxicity of immune cells towards tumor cells, and shows significant tumor growth inhibition in vivo. It also activates T-cells and reverses the inhibitory tumor microenvironment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Hyun-Sung Lee, Hee-Jin Jang, Maheshwari Ramineni, Daniel Y. Wang, Daniela Ramos, Jong Min Choi, Taylor Splawn, Monica Espinoza, Michelle Almarez, Leandria Hosey, Eunji Jo, Susan Hilsenbeck, Christopher I. Amos, R. Taylor Ripley, Bryan M. Burt
Summary: This study compared the effects of monotherapy and combination therapy on pathological response and survival in resectable patients. The results showed that combination therapy can alter the immune microenvironment of malignant pleural mesothelioma tumors and improve overall survival.
CLINICAL CANCER RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Patience Setordzi, Xing Chang, Zi Liu, Yingliang Wu, Daiying Zuo
Summary: Research on PD-1/PD-L1 immune checkpoint inhibitors for breast cancer has been active for the past decade, showing promising results in both monotherapy and combination therapy with other inhibitors. These trials have demonstrated improved and sustained therapeutic responses, pointing towards new insights in breast cancer research and the direction of PD-1/PD-L1 immune checkpoint signaling.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Article
Medicine, Research & Experimental
Zhongxi Zhao, Guangwei Wei, Jianxiong Zhao, Yueyue Sun, Peng Gao
Summary: S-allylmercaptocysteine (SAMC) has significant anti-tumor effects and can inhibit inflammation in chronic obstructive pulmonary disease. Our study demonstrates that SAMC enhances anti-tumor immunity by increasing the infiltration of CD8+ T cells and NK cells, decreasing the frequency of Treg cells, and promoting systemic immune function. Mechanistically, SAMC suppresses PD-L1 expression through the STAT3 pathway, leading to the activation of anti-tumor cytotoxic T cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Surgery
Victor P. Gazivoda, Aaron W. Kangas-Dick, Alissa A. Greenbaum, Joshua Roshal, Chunxia Chen, Dirk F. Moore, Russell C. Langan, Timothy J. Kennedy, Christine Minerowicz, H. Richard Alexander
Summary: This study aimed to characterize the frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM). The results showed a high frequency of PD-L1 expression in MPM patients, which may be associated with more aggressive tumor biology. These findings are important for further evaluation of checkpoint inhibition in MPM patients.
JOURNAL OF SURGICAL RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Puey Ling Chia, Andrew M. Scott, Thomas John
EXPERT OPINION ON DRUG DELIVERY
(2019)
Article
Medicine, General & Internal
Zoe Loh, David S. Williams, Lucinda Salmon, Eryn Dow, Thomas John
INTERNAL MEDICINE JOURNAL
(2019)
Article
Cell Biology
Erinna F. Lee, Tiffany J. Harris, Sharon Tran, Marco Evangelista, Surein Arulananda, Thomas John, Celeste Ramnac, Chloe Hobbs, Haoran Zhu, Gency Gunasingh, David Segal, Andreas Behren, Jonathan Cebon, Alexander Dobrovic, John M. Mariadason, Andreas Strasser, Leona Rohrbeck, Nikolas K. Haass, Marco J. Herold, W. Douglas Fairlie
CELL DEATH & DISEASE
(2019)
Article
Oncology
Crescens Tiu, Zoe Loh, ChunLoo Gan, Hui Gan, Thomas John, Eliza Hawkes
Article
Respiratory System
Surein Arulananda, Hongdo Do, Gareth Rivalland, Zoe Loh, Ashan Musafer, Eddie Lau, Paul Mitchell, Alexander Dobrovic, Thomas John
JOURNAL OF THORACIC DISEASE
(2019)
Editorial Material
Oncology
Surein Arulananda, Paul Mitchell, Thomas John
JOURNAL OF THORACIC ONCOLOGY
(2019)
Editorial Material
Pathology
Nick Pavlakis, Caroline Cooper, Thomas John, Steven Kao, Sonja Klebe, Chee Khoon Lee, Trishe Leong, Michael Millward, Ken O'Byrne, Prudence A. Russell, Benjamin Solomon, Wendy A. Cooper, Stephen Fox
Article
Oncology
Peey-Sei Kok, Kirsty Lee, Sally Lord, James Chih-Hsin Yang, Rafael Rosell, Koichi Goto, Thomas John, Yi-Long Wu, Tony S. K. Mok, Chee Khoon Lee
Summary: This study aimed to evaluate the clinical utility of qPCR assays for detection of EGFR mutation in ctDNA of treatment-naive advanced lung cancer patients. Results showed that EGFR-TKI had better progression-free survival, objective response rate, and overall survival compared to chemotherapy in both ctDNA+ and ctDNA- subgroups.
Article
Oncology
Margarita Majem, Jonathan W. Goldman, Thomas John, Christian Grohe, Konstantin Laktionov, Sang-We Kim, Terufumi Kato, Huu Vinh Vu, Shun Lu, Shanqing Li, Kye Young Lee, Charuwan Akewanlop, Chong-Jen Yu, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Shinji Atagi, Lingmin Zeng, Dakshayini Kulkarni, Nenad Medic, Masahiro Tsuboi, Roy S. Herbst, Yi-Long Wu
Summary: This study demonstrated that adjuvant osimertinib treatment maintained health-related quality of life in patients with completely resected EGFR-mutated non-small cell lung cancer, with no clinically meaningful differences compared to placebo.
CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
Rachel Woodford, Deborah Zhou, Sarah J. Lord, Ian Marschner, Wendy A. Cooper, Craig R. Lewis, Thomas John, James Chih-Hsin Yang, Chee Khoon Lee
Summary: High PD-L1 expression in non-small-cell lung cancer (mNSCLC) is associated with longer overall survival and improved response rates to chemotherapy. However, different assay methods may impact the accuracy of these results.
Review
Oncology
Jose Luis Leal, Thomas John
Summary: The treatment paradigm of non-small-cell lung cancer has changed significantly in recent years, with immune-checkpoint inhibitors becoming the standard of care. However, most patients still experience disease progression. This review discusses treatment alternatives after progression and mechanisms of resistance.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
John F. Markham, Andrew P. Fellowes, Thomas Green, Jose Luis Leal, Roxane Legaie, Darren Cullerne, Tessa Morris, Tom John, Ben Solomon, Stephen B. Fox
Summary: This study investigates the use of targeted RNA sequencing to measure tumor mutational burden (TMB) and expression of immune-cell-restricted genes from FFPE specimens, and their predictive value for response to immune checkpoint blockade treatment in NSCLC patients. The results show that TMB calculated from targeted RNA sequencing correlates with TMB derived from DNA sequencing, and it can predict response to immune blockade treatment. However, the expression of immune-cell-restricted genes is not correlated with patient outcome.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S. Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A. Shepherd, Krishna C. Bulusu, Gianluca Laus, Barbara Collins, J. Carl Barrett, Ryan J. Hartmaier, Vassiliki Papadimitrakopoulou
Summary: The third-generation EGFR tyrosine kinase inhibitor osimertinib improves progression-free survival compared to platinum-doublet chemotherapy in patients with advanced NSCLC carrying EGFR T790M mutation. In this study, the authors used next-generation sequencing to evaluate the potential mechanisms of acquired resistance to osimertinib in patients from the AURA3 trial. Some patients had undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation.
NATURE COMMUNICATIONS
(2023)
Article
Respiratory System
Lara Edbrooke, Catherine L. Granger, Jill J. Francis, Tom John, Nasreen Kaadan, Emma Halloran, Bronwen Connolly, Linda Denehy
Summary: This study aims to develop a core set of clinically relevant lung cancer rehabilitation outcomes for use in clinical practice, in order to improve function, health-related quality of life, and manage the high symptom burden associated with lung cancer. The research utilizes an international Delphi consensus study, involving various stakeholders, to determine the priority outcomes for a core outcome set (COS) for lung cancer rehabilitation.
BMJ OPEN RESPIRATORY RESEARCH
(2023)
Editorial Material
Oncology
Hui Jing Hoe, Adithya Balasubramanian, Thomas John
JOURNAL OF THORACIC ONCOLOGY
(2023)