Article
Oncology
Joseph Chao, Charles S. Fuchs, Kohei Shitara, Josep Tabernero, Kei Muro, Eric Van Cutsem, Yung-Jue Bang, Ferdinando De Vita, Gregory Landers, Chia-Jui Yen, Ian Chau, Anneli Elme, Jeeyun Lee, Mustafa Ozguroglu, Daniel Catenacci, Harry H. Yoon, Erluo Chen, David Adelberg, Chie-Schin Shih, Sukrut Shah, Pooja Bhagia, Zev A. Wainberg
Summary: This study indicates that MSI-H status may serve as a biomarker for pembrolizumab therapy in advanced G/GEJ cancer patients regardless of the line of therapy.
Article
Cell Biology
Nigel Scott, Nick P. West, Alison Cairns, Olorunda Rotimi
Summary: Medullary carcinoma of the colon is often mistaken for poorly differentiated adenocarcinoma NOS and occasionally for neuroendocrine or metastatic carcinoma. Greater familiarity with morphological criteria and use of mismatch repair protein staining should improve diagnosis. Most medullary carcinomas exhibit mismatch repair deficiency, are located in ascending colon and caecum and have a lower rate of vascular channel invasion and lymph node metastasis compared to poorly differentiated adenocarcinoma.
Article
Oncology
Christopher J. Schwartz, Edaise M. da Silva, Antonio Marra, Andrea M. Gazzo, Pier Selenica, Vikas K. Rai, Diana Mandelker, Fresia Pareja, Maksym Misyura, Timothy M. D'Alfonso, Edi Brogi, Pamela Drullinsky, Pedram Razavi, Mark E. Robson, Joshua Z. Drago, Hannah Y. Wen, Liying Zhang, Britta Weigelt, Jinru Shia, Jorge S. Reis-Filho, Hong Zhang
Summary: A subset of breast cancers developing in individuals with Lynch syndrome are etiologically linked to MMR deficiency and may benefit from anti-PD1/PD-L1 immunotherapy.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Bernard C. H. Lee, Philip S. Robinson, Tim H. H. Coorens, Helen H. N. Yan, Sigurgeir Olafsson, Henry Lee-Six, Mathijs A. Sanders, Hoi Cheong Siu, James Hewinson, Sarah S. K. Yue, Wai Yin Tsui, Annie S. Y. Chan, Anthony K. W. Chan, Siu Lun Ho, Peter J. Campbell, Inigo Martincorena, Simon J. A. Buczacki, Siu Tsan Yuen, Suet Yi Leung, Michael R. Stratton
Summary: The study shows that normal tissues in Lynch Syndrome (LS) patients are genomically stable, while ancestor cells of neoplastic tissues undergo multiple cycles of clonal evolution. This highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Laura A. Sena, Julia Fountain, Pedro Isaacsson Velho, Su Jin Lim, Hao Wang, Emily Nizialek, Nityam Rathi, Roberto Nussenzveig, Benjamin L. Maughan, Miguel Gonzalez Velez, Ryan Ashkar, Amanda C. Larson, Colin C. Pritchard, Nabil Adra, Alan H. Bryce, Neeraj Agarwal, Drew M. Pardoll, James R. Eshleman, Tamara L. Lotan, Emmanuel S. Antonarakis
Summary: In patients with DNA mismatch repair-deficient prostate cancer, tumor frameshift mutation proportion (FSP) is correlated with response to anti-PD1 therapy.
Article
Oncology
M. Maio, P. A. Ascierto, L. Manzyuk, D. Motola-Kuba, N. Penel, P. A. Cassier, G. M. Bariani, A. De Jesus Acosta, T. Doi, F. Longo, W. H. Jr Jr Miller, D-Y Oh, M. Gottfried, L. Xu, F. Jin, K. Norwood, A. Marabelle
Summary: Pembrolizumab has shown clinically meaningful and durable efficacy in previously treated advanced MSI-H/dMMR noncolorectal cancers, with a high ORR of 30.8%, a median duration of response of 47.5 months, and manageable safety.
ANNALS OF ONCOLOGY
(2022)
Review
Gastroenterology & Hepatology
Ellis L. Eikenboom, Anne-Sophie van der Werf-'t Lam, Mar Rodriguez-Girondo, Christi J. Van Asperen, Winand N. M. Dinjens, Robert M. W. Hofstra, Monique E. Van Leerdam, Hans Morreau, Manon C. W. Spaander, Anja Wagner, Maartje Nielsen
Summary: This study investigates the effectiveness and cost of immunohistochemistry testing in Lynch syndrome patients and their relatives. The proportion of MMRd and MMR germline PV is influenced by age, completeness, and type of diagnostics, and complete diagnostics can explain almost all MMRd CRC, contributing to optimizing testing and surveillance.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yuan Zhuang, Jiangle Liu, Hao Wu, Qingguo Zhu, Yongchang Yan, Haowei Meng, Peng R. Chen, Chengqi Yi
Summary: The HOPE method utilizes paired pegRNAs encoding the same edits to achieve high editing efficiency in human embryonic kidney and colorectal carcinoma cells, showing improved product purity compared to the original PE3 system. This enhanced tool has the potential to broaden both fundamental research and therapeutic applications of prime editing.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Oncology
Richard Gallon, Peter Gawthorpe, Rachel L. Phelps, Christine Hayes, Gillian M. Borthwick, Mauro Santibanez-Koref, Michael S. Jackson, John Burn
Summary: The article discusses international guidelines for the diagnosis of Lynch syndrome (LS), barriers and limitations, as well as new screening opportunities. It also proposes additional LS screening strategies.
Article
Multidisciplinary Sciences
Yunbeom Lee, Ji Ae Lee, Hye Eun Park, Hyojun Han, Yuhnam Kim, Jeong Mo Bae, Jung Ho Kim, Nam-Yun Cho, Hwang-Phill Kim, Tae-You Kim, Gyeong Hoon Kang
Summary: A new computational method and microsatellite marker panels were developed to assess and detect microsatellite instability in CRC, which does not require paired normal tissues. It showed good sensitivity and specificity for different types of samples.
Article
Oncology
Alberto Farolfi, Amelia Altavilla, Luca Morandi, Laura Capelli, Elisa Chiadini, Giovanna Prisinzano, Giorgia Gurioli, Marianna Molari, Daniele Calistri, Maria Pia Foschini, Ugo De Giorgi
Summary: This study examines the relationship between endometriosis and endometrial cancer. Somatic mutation profile and phylogenetic analysis reveal that tumor cells may retrogradely disseminate to the ectopic sites of endometriosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Materials Science, Biomaterials
Chufan Wang, Cheng Xiao, Yurong Chen, Yao Li, Qiang Zhang, Wenjun Shan, Yulin Li, Shengli Bi, Yunlong Wang, Xiumin Wang, Lei Ren
Summary: Protein cages, specifically virus-like particles (VLPs), have shown potential in vaccine development and targeted drug delivery. However, existing protein-based platform technologies often face immunological challenges that hinder their efficiency as drug carriers.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Letter
Gastroenterology & Hepatology
Viktoria Bergqvist, Johanna Holmgren, Daniel Klintman, Jan Marsal
Summary: This article is related to the papers by Bergqvist et al.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Immunology
Pingchao Li, Qian Wang, Yizi He, Chenchen Yang, Zhengyuan Zhang, Zijian Liu, Bo Liu, Li Yin, Yilan Cui, Peiyu Hu, Yichu Liu, Pingqian Zheng, Wei Wang, Linbing Qu, Caijun Sun, Suhua Guan, Liqiang Feng, Ling Chen
Summary: Prolonged infection and possible evolution of SARS-CoV-2 in patients living with uncontrolled HIV-1 infection highlight the importance of an effective vaccination regimen, yet the immunogenicity of COVID-19 vaccines and predictive immune biomarkers have not been well investigated.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Oncology
Stephanie R. Hicks, Amanda K. Cozart, Gary A. Bellus, Kami W. Schneider
Summary: This study explores the phenotypes of individuals with a clinical diagnosis of NF1 to identify subpopulations who may need further genetic counseling or testing for an alternate diagnosis. It found minimal differences in clinical presentation, family history, and cancer history between the at-risk population and the control group, suggesting tiered genetic testing for all individuals being evaluated for NF1 may help identify misdiagnosed patients. Early diagnosis of conditions like constitutional mismatch repair deficiency is crucial for cancer prevention.
CANCER PREVENTION RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Lucy H. Maynard, Olivia Smith, Nicolas P. Tilmans, Eleonore Tham, Shayan Hosseinzadeh, Weilun Tan, Ryan Leenay, Andrew P. May, Nicole K. Paulk
HUMAN GENE THERAPY METHODS
(2019)
Article
Cell Biology
Amy Li, Rebecca H. Herbst, David Canner, Jason M. Schenkel, Olivia C. Smith, Jonathan Y. Kim, Michelle Hillman, Arjun Bhutkar, Michael S. Cuoco, C. Garrett Rappazzo, Patricia Rogers, Celeste Dang, Livnat Jerby-Arnon, Orit Rozenblatt-Rosen, Le Cong, Michael Birnbaum, Aviv Regev, Tyler Jacks
Article
Biology
Natasha D. Durham, Aditi Agrawal, Eric Waltari, Derek Croote, Fabio Zanini, Mallorie Fouch, Edgar Davidson, Olivia Smith, Esteban Carabajal, John E. Pak, Benjamin J. Doranz, Makeda Robinson, Ana M. Sanz, Ludwig L. Albornoz, Fernando Rosso, Shirit Einav, Stephen R. Quake, Krista M. McCutcheon, Leslie Goo
Article
Cell Biology
Jesse D. Kirkpatrick, Andrew D. Warren, Ava P. Soleimany, Peter M. K. Westcott, Justin C. Voog, Carmen Martin-Alonso, Heather E. Fleming, Tuomas Tammela, Tyler Jacks, Sangeeta N. Bhatia
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Oncology
Nemanja Despot Marjanovic, Matan Hofree, Jason E. Chan, David Canner, Katherine Wu, Marianna Trakala, Griffin G. Hartmann, Olivia C. Smith, Jonathan Y. Kim, Kelly Victoria Evans, Anna Hudson, Orr Ashenberg, Caroline B. M. Porter, Alborz Bejnood, Ayshwarya Subramanian, Kenneth Pitter, Yan Yan, Toni Delorey, Devan R. Phillips, Nisargbhai Shah, Ojasvi Chaudhary, Alexander Tsankov, Travis Hollmann, Natasha Rekhtman, Pierre P. Massion, John T. Poirier, Linas Mazutis, Ruifang Li, Joo-Hyeon Lee, Angelika Amon, Charles M. Rudin, Tyler Jacks, Aviv Regev, Tuomas Tammela
Article
Immunology
Jason M. Schenkel, Rebecca H. Herbst, David Canner, Amy Li, Michelle Hillman, Sean-Luc Shanahan, Grace Gibbons, Olivia C. Smith, Jonathan Y. Kim, Peter Westcott, William L. Hwang, William A. Freed-Pastor, George Eng, Michael S. Cuoco, Patricia Rogers, Jin K. Park, Megan L. Burger, Orit Rozenblatt-Rosen, Le Cong, Kristen E. Pauken, Aviv Regev, Tyler Jacks
Summary: In tumors, a subset of CD8(+) T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. As tumors progress, intratumoral TCF-1(+) CD8(+) T cells acquire dysfunctional features and decrease in number, while their frequency in tumor draining LN remains stable. The decrease in conventional type I dendritic cells (cDC1) in dLN contributes to failed anti-tumor immunity by reducing the reservoir of TCF-1(+) CD8(+) T cells.
Article
Cell Biology
Santiago Naranjo, Christina M. Cabana, Lindsay M. LaFave, Rodrigo Romero, Sean-Luc Shanahan, Arjun Bhutkar, Peter M. K. Westcott, Jason M. Schenkel, Arkopravo Ghosh, Laura Z. Liao, Isabella Del Priore, Dian Yang, Tyler Jacks
Summary: In this study, the authors describe optimized conditions for expanding murine alveolar type 2 cells in organoid culture. They used this system to develop immunocompetent organoid-based models of KRAS, BRAF, and ALK mutant LUAD, demonstrating its power and versatility in studying lung cancer.
GENES & DEVELOPMENT
(2022)
Article
Immunology
Noah Gavil, Milcah C. Scott, Eyob Weyu, Olivia C. Smith, Stephen D. O'Flanagan, Sathi Wijeyesinghe, Sahar Lotfi-Emran, Stephen L. Shiao, Vaiva Vezys, David Masopust
Summary: Analyses of healthy tissue show that resident memory CD8(+) T cells (TRM) can be identified, which are able to survey tissues without recirculating. The density of TRM phenotype cells within solid tumors is positively correlated with prognosis, indicating that intratumoral residents can control cancer. However, the residence status has not been directly tested and intratumoral TRM phenotype cells may reflect aspects of the microenvironment that are associated with prognosis. Using a breast cancer model in mice, it was found that conventional TRM markers cannot determine the tumor residence of bystander or tumor-specific cells, which exhibit distinct phenotypes in the tumor microenvironment and healthy mammary tissue. Instead, tumor-specific, stem progenitor CD8(+) T cells migrate to tumors and become resident while acquiring certain markers of exhaustion. These findings suggest that the tumor environment and tonic antigen stimulation drive different programs of residence compared to healthy tissues, and that tumor immunity is sustained by the continuous migration of tumor-specific stem cells.
SCIENCE IMMUNOLOGY
(2023)
Article
Oncology
Peter M. K. Westcott, Nathan J. Sacks, Jason M. Schenkel, Zackery A. Ely, Olivia Smith, Haley Hauck, Alex M. Jaeger, Daniel Zhang, Coralie M. Backlund, Mary C. Beytagh, J. J. Patten, Ryan Elbashir, George Eng, Darrell J. Irvine, Omer H. Yilmaz, Tyler Jacks
Summary: The study reveals that despite low TMB, tumors from patients with microsatellite stable colorectal cancer still express predicted neoantigens, although at lower levels compared to those in colorectal cancer with microsatellite instability. Low expression of neoantigens may lead to immediate T-cell dysfunction, but it can be controlled by restoring priming in tumors with low neoantigen expression.