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
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
Immunology
Jiming Chen, Jie Yang, Wenhui Wang, Danfeng Guo, Chengyan Zhang, Shibo Wang, Xinliang Lu, Xiaofang Huang, Pingli Wang, Gensheng Zhang, Jing Zhang, Jianli Wang, Zhijian Cai
Summary: PD-L1(+) tumor-derived extracellular vesicles (TEVs) cause resistance to anti-PD-L1 antibody therapy by decoying the antibody and being cleared by macrophages, resulting in insufficient blockade of tumor PD-L1.
CELLULAR & MOLECULAR 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)
Review
Oncology
Jihane Boustani, Benoit Lecoester, Jeremy Baude, Charlene Latour, Olivier Adotevi, Celine Mirjolet, Gilles Truc
Summary: Combining radiation therapy with immune checkpoint inhibitors shows synergistic potential in enhancing anti-tumor immune responses, although optimization of treatment requires consideration of factors such as dose, fractionation, target volume, lymph nodes, and other immunomodulatory agents.
Review
Biochemistry & Molecular Biology
Hao Zhang, Lin Liu, Jinbo Liu, Pengyuan Dang, Shengyun Hu, Weitang Yuan, Zhenqiang Sun, Yang Liu, Chengzeng Wang
Summary: In recent years, tumor immunotherapy, especially immune checkpoint inhibitors, has shown significant progress. However, these treatments are only effective for a small proportion of patients with solid cancers. Tumor-associated macrophages play a crucial role in the tumor microenvironment and have been shown to impact the therapeutic effect of PD-1/PD-L1 inhibitors.
Review
Immunology
Yiru Long, Xiaolu Yu, Runqiu Chen, Yongliang Tong, Likun Gong
Summary: With programmed death 1/ligand 1 (PD-1/PD-L1) as the cornerstone, anti-PD antibodies have revolutionized immunotherapies for malignancies. However, many patients fail to respond to anti-PD treatment due to resistance or hyperprogression. The study highlights the importance of noncanonical PD-1/PD-L1 expression in various cancers and its impact on the efficacy of anti-PD antibodies.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Charlotte Margareta Brinch, Estrid Hogdall, Niels Junker, Holger Jon Moeller, Birgitte Sandfeld-Paulsen, Pieter de Heer, Luit Penninga, Philip Blach Rossen, Anders Krarup-Hansen, Ninna Aggerholm-Pedersen
Summary: This study investigates the prognostic value of plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) concentrations in patients with Gastrointestinal Stromal Tumor (GIST). The results show that the plasma concentrations of PD-1 and PD-L1 are associated with the activity of GIST, and high concentration of PD-L1 is related to poor prognosis.
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
Medicine, General & Internal
Christoph Minichsdorfer, Andreas Gleiss, Marie-Bernadette Aretin, Manuela Schmidinger, Thorsten Fuereder
Summary: The results of this analysis suggest that serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type.
ANNALS OF MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Nian Liu, JiangLin Zhang, Mingzhu Yin, Hong Liu, Xu Zhang, Jiaoduan Li, Bei Yan, Yeye Guo, Jianda Zhou, Juan Tao, Shuo Hu, Xiang Chen, Cong Peng
Summary: The study demonstrated that inhibiting xCT may be a promising therapeutic strategy for melanoma, but it also reduces the efficacy of anti-PD-1/PD-L1 treatment by inducing PD-L1 expression and M2 macrophage polarization. Further research is needed to understand the impact of glutamate metabolism on tumor progression and immunotherapy outcomes.
Article
Chemistry, Multidisciplinary
Huihuang Li, Jinbo Chen, Zhenghao Li, Minfeng Chen, Zhenyu Ou, Miao Mo, Ruizhe Wang, Shiyu Tong, Peihua Liu, Zhiyong Cai, Chunyu Zhang, Zhi Liu, Dingshan Deng, Jinhui Liu, Chunliang Cheng, Jiao Hu, Xiongbing Zu
Summary: A systematic multi-omics analysis identified S100A5 as a novel immunosuppressive target for bladder cancer. The expression of S100A5 inhibits CD8(+) T cell recruitment and cytotoxicity, leading to resistance to immune checkpoint blockade therapy. Targeting S100A5 enhances the infiltration and cytotoxicity of CD8(+) T cells, thereby enhancing the efficacy of immune checkpoint blockade therapy in bladder cancer.
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)
Review
Immunology
Luyao Wang, Zongxing Yang, Fucheng Guo, Yurong Chen, Jiarui Wei, Xiangpeng Dai, Xiaoling Zhang
Summary: Currently, anti-PD-1/PD-L1 immunotherapy is widely used for treating lung cancer, but only a limited proportion of patients benefit from it. Therefore, it is important to predict the response to immunotherapy. PD-L1 expression, tumor mutation burden, tumor-specific genes, dMMR/MSI, and gut microbiome have been studied as potential predictors. In addition, invasive blood biomarkers such as ctDNA, immune cells, and cytokines have also been used. This review summarizes the achievements and potential biomarkers for predicting the response to anti-PD-1/PD-L1 immunotherapy in lung cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Nina Kozlova, Joseph E. Grossman, Marcin P. Iwanicki, Taru Muranen
TRENDS IN PHARMACOLOGICAL SCIENCES
(2020)
Article
Medicine, Research & Experimental
Ling Huang, Bruno Bockorny, Indranil Paul, Dipikaa Akshinthala, Pierre-Oliver Frappart, Omar Gandarilla, Arindam Bose, Veronica Sanchez-Gonzalez, Emily E. Rouse, Sylvain D. Lehoux, Nicole Pandell, Christine M. Lim, John G. Clohessy, Joseph Grossman, Raul Gonzalez, Sofia Perea Del Pino, George Daaboul, Mandeep S. Sawhney, Steven D. Freedman, Alexander Kleger, Richard D. Cummings, Andrew Emili, Lakshmi B. Muthuswamy, Manuel Hidalgo, Senthil K. Muthuswamy
Article
Oncology
Joseph E. Grossman, Lakshmi Muthuswamy, Ling Huang, Dipikaa Akshinthala, Sofia Perea, Raul S. Gonzalez, Leo L. Tsai, Jonah Cohen, Bruno Bockorny, Andrea J. Bullock, Benjamin Schlechter, Mary Linton B. Peters, Catherine Conahan, Supraja Narasimhan, Christine Lim, Roger B. Davis, Robert Besaw, Mandeep S. Sawhney, Douglas Pleskow, Tyler M. Berzin, Martin Smith, Tara S. Kent, Mark Callery, Senthil K. Muthuswamy, Manuel Hidalgo
Summary: This pilot feasibility trial investigated the use of patient-derived organoids (PDOs) to guide personalized therapy for pancreatic ductal adenocarcinoma (PDAC). The study found that the drug sensitivity of PDOs can predict the clinical outcome of patients and is correlated with treatment responses.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Qingda Meng, Shanshan Xie, G. Kenneth Gray, Mohammad H. Dezfulian, Weilin Li, Ling Huang, Dipikaa Akshinthala, Elizabeth Ferrer, Catherine Conahan, Sofia Perea Del Pino, Joseph Grossman, Stephen J. Elledge, Manuel Hidalgo, Senthil K. Muthuswamy
Summary: This study reports a platform for expanding tumor-targeting T cells from the peripheral blood of patients with pancreatic cancer, and identifies the NKG2A-HLA-E axis as an important checkpoint for CD8+ T cells in pancreatic cancer. Empirical identification of tumor-targeting TCRs suitable for TCR therapy was demonstrated.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Meeting Abstract
Oncology
Anthony El-Khoueiry, Andrea Bullock, Apostolia Tsimberidou, Daruka Mahadevan, Breelyn Wilky, Przemyslaw Twardowski, Bruno Bockorny, Justin Moser, Waldo Ortuzar Feliu, Joseph Grossman, Katherine Rosenthal, Steven O'Day, Michael Gordon
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Meeting Abstract
Oncology
A. Bullock, J. Grossman, M. Fakih, H. Lenz, M. Gordon, K. Margolin, B. Wilky, D. Mahadevan, J. Trent, B. Bockorny, J. Moser, A. Balmanoukian, B. Schlechter, W. Ortuzar Feliu, K. Rosenthal, B. Bullock, J. Stebbing, J. Godwin, S. O'Day, A. Tsimberidou, A. El-Khoueiry
ANNALS OF ONCOLOGY
(2022)
Review
Oncology
Bruno Bockorny, Joseph E. Grossman, Manuel Hidalgo
Summary: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging cancer to treat. Chemotherapy has limited benefits and immunotherapy has made little progress. However, recent advances in understanding the tumor microenvironment and new approaches to immunotherapy have provided hope. Improvements in preclinical models, targeting the tumor microenvironment, and identifying biomarkers will likely lead to better selection of patients who could benefit from immunotherapy. Urgent research is needed to design effective combination trials to cure patients with PDAC.
CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Oncology
David M. Faleck, Michael Dougan, Monique Tello, Joseph E. Grossman, Alan C. Moss, Michael A. Postow
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T. H. Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P. Rocca, Allyson J. Ocean, Elizabeta C. Popa, Daniel H. Hunt, Nikhil P. Uppal, Kelly A. Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A. Shah, Erika Hissong
Summary: This study reports exceptional responses observed in patients with pMMR/MSS colon and rectal cancer treated with neoadjuvant botensilimab (BOT) and balstilimab (BAL). The findings have important implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.
Article
Biochemistry & Molecular Biology
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T. H. Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P. Rocca, Allyson J. Ocean, Elizabeta C. Popa, Daniel H. Hunt, Nikhil P. Uppal, Kelly A. Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A. Shah, Erika Hissong
Summary: Neoadjuvant botensilimab and balstilimab showed exceptional responses in patients with locally advanced mismatch repair proficient/microsatellite stable colon and rectal cancer. The observed rapid immune response pattern has not been previously described. Spatial biology analyses revealed the mechanism of action of botensilimab.
Article
Oncology
Manuel Hidalgo, Rocio Garcia-Carbonero, Kian-Huat Lim, Wells A. Messersmith, Ignacio Garrido-Laguna, Erkut Borazanci, Andrew M. Lowy, Laura Medina Rodriguez, Daniel Laheru, Beatriz Salvador-Barbero, Marcos Malumbres, David J. Shields, Joseph E. Grossman, Xin Huang, Meggan Tammaro, Jean-Francois Martini, Yanke Yu, Kenneth Kern, Teresa Macarulla
Summary: This study evaluates the clinical efficacy and safety of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma. The preclinical and clinical data suggest that this combination treatment has antitumor activity and tolerable toxicity, but does not meet the prespecified efficacy threshold.
CANCER RESEARCH COMMUNICATIONS
(2022)
Meeting Abstract
Oncology
Joseph Elan Grossman, Andrea J. Bullock, Susana Angarita, Bruno Bockorny, Farshid Dayyani, Molly Hurley, Kimberly McGregor, Eirini Pectasides, Mary Linton Bounetheau Peters, Venkataprasanth P. Reddy, Benjamin L. Schlechter, Mehrad Tavallai, Jessica A. Zerillo
JOURNAL OF CLINICAL ONCOLOGY
(2020)
