Article
Oncology
Daniel J. Olson, Zeynep Eroglu, Bruce Brockstein, Andrew S. Poklepovic, Madhuri Bajaj, Sunil Babu, Sigrun Hallmeyer, Mario Velasco, Jose Lutzky, Emily Higgs, Riyue Bao, Timothy C. Carll, Brian Labadie, Thomas Krausz, Yuanyuan Zha, Theodore Karrison, Vernon K. Sondak, Thomas F. Gajewski, Nikhil Khushalani, Jason J. Luke
Summary: This study is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.
JOURNAL OF CLINICAL ONCOLOGY
(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
Oncology
H. Ueki, N. Hinata, K. Kitagawa, T. Hara, T. Terakawa, J. Furukawa, K. Harada, Y. Nakano, M. Komatsu, M. Fujisawa, T. Shirakawa
Summary: This study found that positive PD-L1 expression in tumor cells in UC patients treated with pembrolizumab was associated with worse overall survival, progression-free survival, and lower disease control rate. In contrast, strong expression of Nectin-4 in tumor cells was correlated with higher disease control rate. PD-L1 and Nectin-4 expression in tumor cells could serve as prognostic biomarkers for predicting the therapeutic effects of pembrolizumab in advanced UC patients.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2022)
Article
Immunology
Eun-Ji Lee, Ji Hye Kim, Tae In Kim, Yeon-Ji Kim, Malk Eun Pak, Chang Hyun Jeon, Yeo Jin Park, Wei Li, Young Soo Kim, Jang-Gi Choi, Hwan-Suck Chung
Summary: This study demonstrates the anticancer effects of Sanguisorbae Radix extract (SRE) through PD-1/PD-L1 blockade and the enhanced immuno-oncologic effects of combination therapy with SRE and pembrolizumab.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Joseph Mabbitt, Ian D. Holyer, James A. Roper, Ulf J. Nilsson, Fredrik R. Zetterberg, Lynda Vuong, Alison C. Mackinnon, Anders Pedersen, Robert J. Slack
Summary: This study found that Gal-3 can enhance the PD-1/PD-L1 immune axis and potentially contribute to immunosuppressive signaling mechanisms within the tumor microenvironment. Additionally, Gal-3 prevents atezolizumab and pembrolizumab from engaging with their respective immune checkpoint receptors. Reversal of this effect with the clinical candidate GB1211 offers a potential enhancing combination therapeutic with anti-PD-1 and -PD-L1 blocking antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Li Wang, John P. Sfakianos, Kristin G. Beaumont, Guray Akturk, Amir Horowitz, Robert P. Sebra, Adam M. Farkas, Sacha Gnjatic, Austin Hake, Sudeh Izadmehr, Peter Wiklund, William K. Oh, Peter M. Szabo, Megan Wind-Rotolo, Keziban Unsal-Kacmaz, Xin Yao, Eric Schadt, Padmanee Sharma, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky
Summary: The study identified dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer, including an adaptive immune response gene signature linked to response and a protumorigenic inflammation gene signature related to resistance. The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer, with a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood samples.
CLINICAL CANCER RESEARCH
(2021)
Review
Immunology
Mengke Niu, Yiming Liu, Ming Yi, Dechao Jiao, Kongming Wu
Summary: The immune checkpoint pathway involving PD-1 and PD-L1 plays a crucial role in inhibiting T-cell proliferation and function, affecting antitumor immune responses. Alternative forms of PD-1/PD-L1, such as sPD-1/sPD-L1 and exoPD-L1, have been detected in cancer patients and may have significant biological activities.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Quanqing Tang, Shihao Li, Gaozhen Huang, Hongwei Liu
Summary: Urothelial carcinoma (UC) is a common malignant tumor. Platinum-based chemotherapy has been the standard treatment for metastatic UC, but immune checkpoint inhibitors (ICIs) offer hope for patients unfit for platinum therapy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Florus C. de Jong, Vera C. Rutten, Tahlita C. M. Zuiverloon, Dan Theodorescu
Summary: PD-1/PD-L1 immune checkpoint inhibitors show promise in high-risk non-muscle invasive bladder cancer and muscle-invasive bladder cancer, but challenges such as biomarkers for response stratification and potentially synergistic combination therapy regimens with PD-1/PD-L1 blockade need to be addressed to improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Review
Nutrition & Dietetics
Samia S. Messeha, Najla O. Zarmouh, Karam F. A. Soliman
Summary: Research on dietary polyphenolic compounds as antitumor agents is increasing due to the link between immunity and cancer. These compounds affect cancer progression and metastasis by inhibiting the EMT process, potentially reducing the risk of breast cancer.
Review
Oncology
Laure Chardin, Alexandra Leary
Summary: Ovarian cancer is a highly lethal gynecologic malignancy with a high recurrence rate, despite many patients responding effectively to current treatments. In order to improve outcomes, further research into the immune microenvironment and the development of effective therapies are urgently needed.
FRONTIERS IN ONCOLOGY
(2021)
Review
Cell Biology
Mateusz Kciuk, Damian Kolat, Zaneta Kaluzinska-Kolat, Mateusz Gawrysiak, Rafal Drozda, Ismail Celik, Renata Kontek
Summary: The application of immunotherapy for cancer treatment is expanding rapidly. Combining immunotherapeutic agents with different treatments can enhance the clinical response in patients who have developed resistance to monotherapy. Chemotherapeutic drugs that induce DNA damage often increase the expression of PD-L1, which can be used by cancer cells to evade immune surveillance. Targeting PD-L1 on cancer cells can restore the immune-reactive tumor microenvironment, making the tumor more susceptible to combined therapies. This review discusses the recent advances in understanding how DDR regulates PD-L1 expression and the impact of certain chemotherapeutic drugs on the anti-tumor immune response.
Review
Biochemistry & Molecular Biology
Hikaru Nanamori, Yu Sawada
Summary: Malignant melanoma is a skin cancer with unfavorable clinical behavior, and immunotherapy is currently used for treatment. However, not all patients can benefit from this therapy. To overcome this limitation, clinicians have focused on epigenetic modification, which may have additional therapeutic efficacy by regulating gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Ali Razaghi, Mickael Durand-Dubief, Nele Brusselaers, Mikael Bjornstedt
Summary: PD-1 and PD-L1 play crucial roles in immune regulation and can be targeted for cancer treatment. Blocking PD-1/PD-L1 can enhance tumor recognition by activated T cells and combining it with type I interferon (IFN) can further improve therapeutic efficacy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Vishal Navani, J. Connor Wells, Devon J. Boyne, Winson Y. Cheung, Darren M. Brenner, Bradley A. McGregor, Chris Labaki, Andrew L. Schmidt, Rana R. McKay, Luis Meza, Sumanta K. Pal, Frede Donskov, Benoit Beuselinck, Maxwell Otiato, Lisa Ludwig, Thomas Powles, Bernadett E. Szabados, Toni K. Choueiri, Daniel Y. C. Heng
Summary: Limited data exists regarding the efficacy of cabozantinib following contemporary first line therapy options in advanced kidney cancer. A real world database analysis of 346 patients revealed clinically meaningful activity of second line cabozantinib after all evaluated contemporary first line therapies, including immune checkpoint blockade combination approaches.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Urology & Nephrology
Heather L. Huelster, Andrew Chang, Kyle M. Rose, Marco Bandini, Maarten Albersen, Eduard Roussel, Juan Chipollini, Yao Zhu, Ding-Wei Ye, Antonio A. Ornellas, Mario Catanzaro, Laura Marandino, Filippo Pederzoli, Oliver W. Hakenberg, Axel Heidenreich, Friederike Haidl, Nick Watkin, Michael Ager, Mohamed E. Ahmed, Jeffrey R. Karnes, Alberto Briganti, Youngchul Kim, Francesco Montorsi, Andrea Necchi, Philippe E. Spiess
Summary: For patients with clinically node positive penile squamous cell carcinoma, performing inguinal lymph node dissection at the same time as tumor resection or in a staged manner does not significantly affect recurrence and survival outcomes.
JOURNAL OF UROLOGY
(2023)
Article
Oncology
Giuseppe Rosiello, Alessandro Larcher, Giuseppe Fallara, Daniele Cignoli, Chiara Re, Alberto Martini, Zhe Tian, Pierre I. Karakiewicz, Alexandre Mottrie, Mattia Boarin, Giulia Villa, Francesco Trevisani, Laura Marandino, Daniele Raggi, Andrea Necchi, Roberto Bertini, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Umberto Capitanio
Summary: Frailty status is associated with increased risk of adverse surgical outcomes and renal function decline after partial nephrectomy for renal cell carcinoma. Frail patients also have a higher risk of mortality due to other causes. However, frailty does not affect the risk of cancer-specific mortality.
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2023)
Article
Multidisciplinary Sciences
A. Gordon Robertson, Khyati Meghani, Lauren Folgosa Cooley, Kimberly A. McLaughlin, Leigh Ann Fall, Yanni Yu, Mauro A. A. Castro, Clarice S. Groeneveld, Aurelien de Reynies, Vadim I. Nazarov, Vasily O. Tsvetkov, Bonnie Choy, Daniele Raggi, Laura Marandino, Francesco Montorsi, Thomas Powles, Andrea Necchi, Joshua J. Meeks
Summary: Checkpoint immunotherapy (CPI) has shown efficacy in some advanced-stage bladder cancer patients, but not all. By analyzing tumor and immune microenvironment in pre- and post-treatment tumors, researchers identified genetic and transcriptomic programs associated with response or resistance to CPI. They also discovered that inhibiting the histone demethylase KDM5B enhances immunogenicity in certain subtypes of bladder cancer.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Urology & Nephrology
Antony Pellegrino, Elio Mazzone, Giorgio Gandaglia, Andrea Necchi, Daniele Raggi, Laura Marandino, Armando Stabile, Vito Cucchiara, Marco Bandini, Giuseppe Rosiello, Gabriele Sorce, Francesco Pellegrino, Simone Scuderi, Daniele Robesti, Mario de Angelis, Mattia Longoni, Pietro Scilipoti, Francesco Montorsi, Alberto Briganti
JOURNAL OF UROLOGY
(2023)
Meeting Abstract
Urology & Nephrology
Chiara Re, Federico Belladelli, Francesco Cei, Lucia Salerno, Sara Cusano, Floriana Iannace, Giovanni Battista Pipitone, Paola Carrera, Annalisa Russo Raucci, Maria Grazia Patricelli, Andrea Falini, Francesco De Cobelli, Pietro Mortini, Francesco Bandello, Rosangela Lattanzio, Massimo Falconi, Stefano Partelli, Andrea Necchi, Laura Marandino, Irene Franco, Isaline Rowe, Francesco Montorsi, Umberto Capitanio, Alessandro Larcher, Andrea Salonia
JOURNAL OF UROLOGY
(2023)
Meeting Abstract
Urology & Nephrology
Daniele Robesti, Luigi Nocera, Federico Belladelli, Julianne G. Schultz, Giuseppe Fallara, Laura Marandino, Daniele Raggi, Francesco Montorsi, Andrea Necchi, Alberto Martini
JOURNAL OF UROLOGY
(2023)
Meeting Abstract
Urology & Nephrology
Siamak Daneshmand, Michiel S. van der Heijden, Joseph M. Jacob, Andrea Necchi, Evanguelos Xylinas, David S. Morris, Philip Spiegelhalder, Daniel Zainfeld, Taek Won Kang, Justin T. Matulay, Laurence H. Belkoff, Karel Decaestecker, Harm Arentsen, Shalaka Hampras, Shu Jin, Christopher J. Cutie, Hussein Sweiti, Katherine Stromberg, Jason Martin, Giuseppe Simone
JOURNAL OF UROLOGY
(2023)
Meeting Abstract
Urology & Nephrology
G. Basile, R. Leni, C. Re, F. Pellegrino, P. Scilipoti, M. Longoni, D. Cannoletta, A. Necchi, G. Gandaglia, A. Salonia, A. Briganti, F. Montorsi, M. Moschini
Meeting Abstract
Urology & Nephrology
G. Basile, R. Leni, C. Re, F. Pellegrino, G. Avesani, P. Scilipoti, M. Longoni, D. Cannoletta, G. Gandaglia, A. Necchi, A. Salonia, A. Briganti, F. Montorsi, M. Moschini
Article
Urology & Nephrology
Arash Rezazadeh Kalebasty, David J. Benjamin, Yohann Loriot, Dimitrios Papantoniou, Arlene O. Siefker-Radtke, Andrea Necchi, Vahid Naini, Jenna Cody Carcione, Ademi Santiago-Walker, Spyros Triantos, Earle F. Burgess
Summary: This study analyzed the clinical outcomes of patients with locally advanced or metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa+) who received anti-PD-(L)1 therapy, and found that FGFRa+ patients may have poorer outcomes compared to FGFRa- patients.
EUROPEAN UROLOGY OPEN SCIENCE
(2023)
Letter
Oncology
Marco Bandini, Alessandro Nini, Alberto Briganti, Andrea Necchi, Francesco Montorsi
Letter
Oncology
Thomas Powles, Joseph E. Burgents, Lei Xu, Toni K. Choueiri
Article
Oncology
Sean M. Hacking, Dean Pavlick, Yihong Wang, Benedito A. Carneiro, Matthew Mullally, Shaolei Lu, Mariana Canepa, Gennady Bratslavsky, Joseph Jacob, Andrea Necchi, Philippe E. Spiess, Li Wang, Evgeny Yakirevich, Jeffrey Ross
Summary: Genomic alterations in NF2 tumor-suppressor gene are associated with aggressive behavior in kidney tumors. NF2 mutations are more frequent in certain histologic subtypes, such as cdRCC, sRCC, uRCC, and pRCC. These tumors also harbor co-occurring genomic alterations in other genes, and have higher expression of PD-L1, suggesting potential sensitivity to immune checkpoint inhibitors.
Article
Oncology
Cristiane Decat Bergerot, Jasnoor Malhotra, Paulo Bergerot, Errol J. Philip, Daniela V. Castro, JoAnn Hsu, Augusto Cesar de Andrade Mota, Andressa Cardoso de Azeredo, Joo Nunes de Matos Neto, Thomas Hutson, Viktor Gruenwald, Axel Bex, Sarah P. Psutka, Brian Rini, Elizabeth R. Plimack, Viraj Master, Laurence Albiges, Toni K. Choueiri, Sumanta Pal, Thomas Powles
Summary: This study explored the perceived relevance of items in the FKSI-19 questionnaire among patients with mRCC. The most relevant items were fatigue, lack of energy, and worry about disease progression, while least relevant items included blood in urine, fevers, and lack of appetite. Patients also raised additional issues related to emotional and physical symptoms, family, treatment effectiveness, spirituality, and financial toxicity.