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
Chemistry, Multidisciplinary
Zhiyong Cai, Jinbo Chen, Zhengzheng Yu, Huihuang Li, Zhi Liu, Dingshan Deng, Jinhui Liu, Chunliang Chen, Chunyu Zhang, Zhenyu Ou, Minfeng Chen, Jiao Hu, Xiongbing Zu
Summary: In order to improve the response rate of immune checkpoint blockade monotherapy (ICB), it is important to identify a potential target for combination therapy. Based on the analysis of tumor microenvironment (TME)-related indicators, it is confirmed that BCAT2 plays a role in shaping a noninflamed TME in bladder cancer. Multiomics analysis reveals that BCAT2 inhibits the recruitment of cytotoxic lymphocytes by suppressing proinflammatory cytokine/chemokine-related pathways and the T-cell-chemotaxis pathway. Immunoassays demonstrate a negative correlation between the secretion of CD8(+)T-cell-related chemokines and BCAT2, resulting in a decrease in the number of CD8(+)T cells around BCAT2(+) tumor cells. The combination of BCAT2 deficiency and anti-PD-1 antibody shows a synergistic effect in vivo, suggesting the potential of BCAT2 in combination therapy. Furthermore, the predictive value of BCAT2 in immunotherapy efficacy is validated in multiple immunotherapy cohorts.
Article
Oncology
LeAnne Young, Shanda Finnigan, Howard Streicher, Helen X. Chen, James Murray, H. Nida Sen, Elad Sharon
Summary: Ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, but can be severe enough to cause treatment discontinuation or delay. Proper evaluation by eye specialists is necessary in managing these adverse events.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Miok Kim, Yong Ki Min, Jinho Jang, Hyejin Park, Semin Lee, Chang Hoon Lee
Summary: This study reveals the distinct immune modulation effects of CD73 inhibition compared to PD-1 blockade, suggesting that AB680 may serve as a novel anticancer immunotherapy for CRC with potential synergistic effects when combined with PD-1 blockers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Junjie Liu, Haisu Tao, Tong Yuan, Jiang Li, Jian Li, Huifang Liang, Zhiyong Huang, Erlei Zhang
Summary: Anti-PD-1/PD-L1 therapy is an effective strategy for cancer treatment, but drug resistance is a challenge. Combining this therapy with regorafenib can enhance its efficacy. Regorafenib modifies the tumor microenvironment through various mechanisms and has immunomodulatory effects on immune cells and tumor cells. Studies on the synergistic mechanism of combination therapy can improve cancer treatment and patient selection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Corinna U. Keber, Marcus Derigs, Carolin Schultz, Moritz Wegner, Susanne Lingelbach, Viktoria Wischmann, Rainer Hofmann, Carsten Denkert, Axel Hegele, Joerg Haenze
Summary: Immune checkpoint blockade therapy is a treatment option for metastatic cancer, and the expression levels of PD-L1 and PD-1 can be used to assess surrogate biomarkers. sPD-L1 in blood may primarily come from peripheral blood cells rather than tumor tissue.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Cell Biology
Yuyin Fu, Yujia Peng, Shengyan Zhao, Jun Mou, Lishi Zeng, Xiaohua Jiang, Chengli Yang, Cheng Huang, Yuyan Li, Yin Lu, Mengdan Wu, Yanfang Yang, Ting Kong, Qinhuai Lai, Yangping Wu, Yuqin Yao, Yuxi Wang, Lantu Gou, Jinliang Yang
Summary: The study suggests that a novel combination therapy utilizing both Foretinib and anti-PD-1 antibody has significant therapeutic effects on CRC, improving tumor growth inhibition, tumor regression rates, and overall survival by reshaping the tumor microenvironment and enhancing anti-tumor immunity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Sho Isoyama, Shigeyuki Mori, Daisuke Sugiyama, Yasuhiro Kojima, Yasuko Tada, Kohei Shitara, Kunihiko Hinohara, Shingo Dan, Hiroyoshi Nishikawa
Summary: Combination therapy of PI3K inhibitor with ICB optimizes T cell activation signaling for antitumor immunity by decreasing Tregs and optimizing memory CD8(+) T cell responses, showing promising potential for cancer treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Zihan Zhao, Siyang Liu, Rui Sun, Wenjie Zhu, Yulin Zhang, Tianyao Liu, Tianhang Li, Ning Jiang, Hongqian Guo, Rong Yang
Summary: Bladder cancer is a highly malignant tumor with limited improvement in prognosis and survival rates. Immune checkpoint inhibitors have revolutionized the treatment of bladder cancer, but their clinical application is limited by low response rates. This study investigated the combination of oxaliplatin and anti-PD-1 inhibitor in bladder cancer mouse models and found that this combination therapy was more efficient than medication alone.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Valentin Vautrot, Hafidha Bentayeb, Sebastien Causse, Carmen Garrido, Jessica Gobbo
Summary: Immunotherapy, particularly through the blockade of immune checkpoints such as PD-1/PD-L1, has become increasingly important in cancer treatment by reactivating the immune system to fight cancer cells. However, resistance to these treatments in a certain proportion of patients has led to efforts to combine PD-1/PD-L1 immunotherapy with targeting other immune checkpoints to improve outcomes. Exosomes, small vesicles secreted by various cells including tumor cells, play a key role in mediating immune resistance and establishing metastatic niches. Research on specific exosomal proteins like PD-L1, CTLA-4, TIM-3, CD73/39, LAG-3, and TIGIT aims to enhance understanding of tumor resistance mechanisms and guide therapeutic decisions in immunotherapy.
Article
Oncology
Pashtoon Murtaza Kasi, Griffin Budde, Michael Krainock, Vasily N. Aushev, Allyson Koyen Malashevich, Meenakshi Malhotra, Perry Olshan, Paul R. Billings, Alexey Aleshin
Summary: This study demonstrates the potential of immune checkpoint inhibitors in treating dMMR/MSI-H colorectal cancer. The case series shows that combination therapy with nivolumab and ipilimumab can achieve a durable response in patients who have progressed on pembrolizumab monotherapy. The use of ctDNA kinetics as a dynamic marker for therapy response assessment is supported by the findings.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Tian Zhang, Patrick M. Forde, Ryan J. Sullivan, Elad Sharon, Elizabeth Barksdale, Wendy Selig, Scot Ebbinghaus, Gina Fusaro, Damla Gunenc, Dena Battle, Robyn Burns, Marc S. Hurlbert, Mark Stewart, Michael B. Atkins
Summary: With the increasing use of PD-(L)1 inhibitors in different treatment settings, there is a significant need to overcome resistance and provide clinical benefits for patients. This manuscript presents key discussion themes and positions reached through a year-long effort, focusing on eligibility criteria, comparators, endpoints, and trial design options for combination therapies in melanoma, NSCLC, or RCC patients after PD-(L)1 pathway blockade.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Jamaal L. James, Brandie C. Taylor, Margaret L. Axelrod, Xiaopeng Sun, Lindsey N. Guerin, Paula Gonzalez-Ericsson, Yu Wang, Violeta Sanchez, Catherine C. Fahey, Melinda E. Sanders, Yaomin Xu, Emily Hodges, Douglas B. Johnson, Justin M. Balko
Summary: This study investigates the predictive role of upregulation of tumor-specific major histocompatibility complex-II (tsMHC-II) in anti-PD-1/PD-L1 therapy, and identifies the inhibitory effects of polycomb repressive complex 2 (PRC2)/EZH2 signaling and H3K27 hypermethylation on tsMHC-II expression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Xuan Zhao, Yulin Bao, Bi Meng, Zijian Xu, Sijin Li, Xu Wang, Rui Hou, Wen Ma, Dan Liu, Junnian Zheng, Ming Shi
Summary: Developing biomarkers for predicting the efficacy of immune checkpoint inhibitor therapies is important for avoiding side effects and economic burden. Current assays evaluating PD-L1 expression are imperfect, but recent studies are advancing the methodologies to improve accuracy. This includes standardization of immunohistochemistry tests and the use of novel in vivo probes and liquid biopsy. Considering PD-L1 expression on non-tumor cells and utilizing artificial intelligence can further enhance the predictive accuracy of PD-L1 as a biomarker.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Fu-xue Huang, Jun-wan Wu, Xia-qin Cheng, Jiu-hong Wang, Xi-zhi Wen, Jing-jing Li, Qiong Zhang, Hang Jiang, Qiu-yue Ding, Xiao-feng Zhu, Xiao-shi Zhang, Ya Ding, Dan-dan Li
Summary: This study showed that high expression of HHLA2 is associated with better prognosis and improved response to immune checkpoint blockades in melanoma patients. The expression of HHLA2 is also positively correlated with the density of CD8(+) tumor infiltrating lymphocytes.
FRONTIERS IN IMMUNOLOGY
(2022)