Article
Immunology
Jie Liu, Jiangfan Xu, Tong Zhang, Kailong Xu, Peihua Bao, Zhibo Zhang, Kaiwen Xue, Ruyi He, Lixin Ma, Yang Wang
Summary: This study provides insights into the immune characteristics of clear cell renal cell carcinoma (ccRCC) using single-cell transcriptomic profiling, revealing an increase in T-cell and myeloid populations and a decrease in B-cell population in tumor tissue compared to normal tissue. Marker genes associated with specific cell types were identified, contributing to a deeper understanding of the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Jiaming Su, Lu Zhou, Zhe Zhang, Xue Xiao, Yanning Qin, Xiaoying Zhou, Tingting Huang
Summary: There has been a significant improvement in prognosis for metastatic renal cell carcinoma (mRCC) patients due to the development and use of immunotherapy. However, there are still controversies and challenges in individualized treatment regarding immunotherapy, and many patients do not respond or develop resistance to immune checkpoint inhibitors (ICIs). Immune-related toxicities are also a concern. Therefore, reliable biomarkers are urgently needed to predict immunotherapeutic outcomes for mRCC patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Weimin Zhong, Fengling Zhang, Chaoqun Huang, Yao Lin, Jiyi Huang
Summary: The study investigated the expression profile of tumor suppressor genes (TSGs) and its clinical response in clear cell renal cell carcinoma (ccRCC), identifying three molecular subtypes associated with immune infiltration levels and survival outcomes. Different subtypes showed varying sensitivity to treatment drugs and immunotherapy, providing potential guidelines for developing novel treatment strategies for ccRCC.
Article
Biochemistry & Molecular Biology
Ji Hyun Lee, Soohyun Hwang, ByulA Jee, Jae-Hun Kim, Jihwan Lee, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Se Hoon Park, Ghee Young Kwon, Minyong Kang
Summary: The study aimed to determine the prognosis of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Retrospective analysis of data from 60 patients showed that patients with subcutaneous fat (SF) loss had shorter overall survival (OS) and progression-free survival (PFS) than those without SF loss. Delta SF was independently associated with OS and PFS, with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57% respectively. Therefore, SF loss after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
David A. Schoenfeld, Myrto Moutafi, Sandra Martinez, Dijana Djureinovic, Ross D. Merkin, Adebowale Adeniran, David A. Braun, Sabina Signoretti, Toni K. Choueiri, Fabio Parisi, Michael Hurwitz, David L. Rimm, Wei Wei, Lucia Jilaveanu, Harriet M. Kluger
Summary: This study used digital spatial profiling to analyze the tumor microenvironment in renal cell carcinoma (RCC) and found lower levels of immune activation markers and changes in macrophages in RCC metastases, including brain metastases. These findings have important implications for future biomarker and treatment studies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Jasna Deluce, Saman Maleki Vareki, Ricardo Fernandes
Summary: The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the treatment of metastatic renal cell carcinomas (mRCC), but a large number of patients still do not respond to this treatment. Furthermore, ICIs can cause immune-related adverse events, which limit their use. Therefore, it is important to identify predictive biomarkers for both efficacy and toxicity associated with ICIs in order to personalize treatment and aid clinical decision-making.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)
Article
Oncology
Alexander Chehrazi-Raffle, Luis Meza, Marice Alcantara, Nazli Dizman, Paulo Bergerot, Nicholas Salgia, JoAnn Hsu, Nora Ruel, Sabrina Salgia, Jasnoor Malhotra, Ewa Karczewska, Marcin Kortylewski, Sumanta Pal
Summary: This study found that specific plasma cytokines were associated with clinical benefit in patients with renal cell carcinoma receiving VEGF-TKI or ICI therapy. These findings support further investigation into plasma cytokines as potential biomarkers for renal cell carcinoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Jacqueline T. Brown, Yuan Liu, Julie M. Shabto, Dylan Martini, Deepak Ravindranathan, Emilie Elise Hitron, Greta Anne Russler, Sarah Caulfield, Lauren Yantorni, Shreyas Subhash Joshi, Haydn Kissick, Kenneth Ogan, Bassel Nazha, Bradley C. Carthon, Omer Kucuk, Wayne B. Harris, Viraj A. Master, Mehmet Asim Bilen
Summary: The modified Glasgow Prognostic Score (mGPS) is a useful biomarker in predicting outcomes for patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitors (ICI). A baseline mGPS of 2 was associated with shorter overall survival (OS) and progression-free survival (PFS), and its discrimination power in predicting survival outcomes was comparable to the IMDC risk score. Additional external and prospective validation of these findings is warranted.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Robin Reschke, Jovian Yu, Blake Flood, Emily F. Higgs, Ken Hatogai, Thomas F. Gajewski
Summary: In human melanoma metastases, CD45(+) cells and Sox10(+) cells are identified as the major cellular sources for CXCL10. CXCL10 within the tumor site serves as a positive prognostic factor for response to immunotherapy, and the use of RNAscope technique is feasible in paraffin tissue. Strategies supporting effector T cell recruitment through the induction of CXCL10 may enhance the efficacy of immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Yuli Jian, Kangkang Yang, Xiaoxin Sun, Jun Zhao, Kai Huang, Abdullah Aldanakh, Zhongyang Xu, Haotian Wu, Qiwei Xu, Lin Zhang, Chunyan Xu, Deyong Yang, Shujing Wang
Summary: Renal cell carcinoma is a highly heterogeneous cancer group, with immune evasion being a hot topic in current research. Immunotherapy is considered the best treatment option for patients with metastatic or advanced renal cell carcinoma, and combination immunotherapy shows promising prospects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Liu-xun Chen, Shen-jie Zeng, Xv-dong Liu, Hai-bin Tang, Jia-wu Wang, Qing Jiang
Summary: This study characterizes the intercellular communications within the ccRCC microenvironment and shows their impact on prognosis and immunotherapy efficacy. It reveals a potential relationship between the VHL phenotype and the landscape of cell-cell communication. Moreover, these communication molecules also influence the development and infiltration of T cells and myeloid cells. Different clusters of intercellular communications have significant predictive value for prognosis and distinguish immunotherapy efficiency.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Lin Yang, Xiaoyu Wang, Jiahao Liu, Xiaoqiang Liu, Sheng Li, Fuchun Zheng, Qianxi Dong, Songhui Xu, Jing Xiong, Bin Fu
Summary: This study aimed to reveal the prognostic and immunological features of ccRCC by using crosstalk genes of lactylation and m6A modification. Screening lactylation-related genes and identifying genes associated with M6A, ccRCC subtypes were identified and a risk model was constructed. The study found higher immune scores, elevated tumor mutational burden, and microsatellite instability scores in the high-risk group, indicating the potential benefits of immunotherapy for these patients. The study also developed a precise prognostic nomogram and identified HIBCH as a potential biomarker for ccRCC. Overall, the study is important for predicting prognosis and identifying therapeutic targets for ccRCC.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Songchen Han, Wenbo Yang, Caipeng Qin, Yiqing Du, Mengting Ding, Huaqi Yin, Tao Xu
Summary: Intratumoral fibrosis in renal clear cell carcinoma (ccRCC) is found to be associated with the immune infiltration of the tumor. The study identifies proteins involved in immunity and tumor-infiltrating lymphocytes that are associated with intratumoral fibrosis. Additionally, the study reveals a negative correlation between the expression of CTLA4 protein and collagen level in ccRCC.
Article
Biochemistry & Molecular Biology
Bin Zheng, Fang Xie, Fajuan Cheng, Jianwei Wang, Zhongshun Yao, Wei He, Zhihong Niu
Summary: This study comprehensively assessed the tumor microenvironment of kidney cancer, identified two immune-related hub genes - IGLL5 and IL2RA, and validated their clinical application value in ccRCC and pRCC. Drug response was also predicted based on selected genes, revealing novel drug candidates for RCC treatment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Cell Biology
Jonathan Anker, Justin Miller, Nicole Taylor, Natasha Kyprianou, Che-Kai Tsao
Summary: Immunotherapy has revolutionized the treatment of many cancer types, with particular progress seen in the treatment of renal cell carcinoma. While clinical benefit from immunotherapy is limited to certain patients, combination-based approaches have shown improved outcomes. Ongoing translational work has helped illuminate response mechanisms and resistance to immunotherapy, shaping the future of treatment for RCC.
Article
Immunology
Iva Lelios, Sebastian A. Stifter, Virginia Cecconi, Ekaterina Petrova, Mirjam Lutz, Dilay Cansever, Sebastian G. Utz, Burkhard Becher, Maries van den Broek, Melanie Greter
Summary: The research found that monocytes play a critical role in promoting UV-induced cutaneous squamous cell carcinoma, while Langerhans cells and dermal macrophages have negligible contribution to tumor formation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Bettina Sobottka, Ronny Nienhold, Marta Nowak, Juergen Hench, Pirmin Haeuptle, Angela Frank, Melanie Sachs, Abdullah Kahraman, Holger Moch, Viktor H. Koelzer, Kirsten D. Mertz
Summary: The study revealed differences in CD8(+) tumor-infiltrating T cell frequencies, TLS presence, and PD-L1 expression between responders and nonresponders to immune checkpoint inhibitors in clear cell renal cell carcinoma patients. However, tumor-specific genetic alterations and gene expression profiles did not correlate with response to ICI.
JOURNAL OF IMMUNOTHERAPY
(2022)
Article
Immunology
Fabio Pagliarulo, Phil F. Cheng, Laurin Brugger, Nick van Dijk, Michiel van den Heijden, Mitchell P. Levesque, Karina Silina, Maries van den Broek
Summary: Lymphoid neogenesis in muscle invasive bladder cancer (MIBC) leads to the formation of tertiary lymphoid structures (TLS) in the tumor microenvironment (TME), which have positive prognostic and predictive associations. This study found that high TLS density, when combined with tumor mutational burden, serves as a novel independent prognostic biomarker in MIBC. Tumors with high TLS density showed increased gene signatures and infiltration of activated lymphocytes, particularly B-cell and CD8(+) T-cell co-infiltration. The study also identified TLS maturation subtypes, although TLS composition appeared to be influenced by the TME rather than the maturation status.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Jaspreet Kaur, Darshan S. Chandrashekar, Zsuzsanna Varga, Bettina Sobottka, Emiel Janssen, Jeanne Kowalski, Umay Kiraz, Sooryanarayana Varambally, Ritu Aneja
Summary: In this study, the researchers used RNA sequencing to compare the gene expression profiles between primary and metastatic tumors of triple-negative breast cancer (TNBC). They identified potential therapeutic targets and revealed the heterogeneity of gene expression patterns related to metastasis.
Article
Biochemical Research Methods
Anne Bertolini, Michael Prummer, Mustafa Anil Tuncel, Ulrike Menzel, Maria Lourdes Rosano-Gonzalez, Jack Kuipers, Daniel Johannes Stekhoven, Niko Beerenwinkel, Franziska Singer
Summary: Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding tissue composition and disease mechanisms at the single-cell level. However, analyzing and interpreting the large amounts of data generated by scRNA-seq is challenging. In this study, we developed a workflow called scAmpi (Single Cell Analysis mRNA pipeline) that processes and analyzes scRNA-seq data from raw sequencing to provide clinically relevant information. The workflow removes low quality cells, identifies cell types, and visualizes gene expression and functional pathways in single cells. Additionally, scAmpi can link gene expression to potential drug candidates for disease treatment.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Sandra Tietscher, Johanna Wagner, Tobias Anzeneder, Claus Langwieder, Martin Rees, Bettina Sobottka, Natalie de Souza, Bernd Bodenmiller
Summary: Immune checkpoint therapy in breast cancer is limited to triple negative patients and shows rare long-term clinical benefit. This study explores the immune environments of human breast tumors with or without exhausted T cells, focusing on luminal subtypes. The presence of a PD-1(high) exhaustion-like T cell phenotype is associated with an inflammatory immune environment, increased myeloid cell activation, elevated immunomodulatory and cytokine signaling, accumulation of natural killer T cells, and altered spatial organization. PD-1 and CXCL13 expression on T cells, and MHC-I expression on tumor cells are distinguishing features between the immune environments.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Oncology
Karina Silina
Summary: Cytotoxic T cells play a crucial role in fighting against most cancers. In the latest issue of Cancer Cell, Gaglia et al. reveal how tumor tissue architecture changes can create niches for T cell-B cell interactions, which may enhance anti-tumor T cell responses.
Article
Oncology
Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.
Review
Urology & Nephrology
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Summary: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that drive antigen-specific immune responses at sites of chronic inflammation. Their presence correlates with disease course, with favorable outcomes in cancer and infection, but more severe disease in autoimmune and chronic inflammatory diseases. However, the mechanisms underlying these associations are still unclear.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Pathology
Aashil A. Batavia, Dorothea Rutishauser, Bettina Sobottka, Peter Schraml, Niko Beerenwinkel, Holger Moch
Summary: This study characterizes 123 renal tumors with clear cell morphology and known VHL mutation status to assess the morphologic and molecular consequences of ELOC inactivation. The presence of ELOC mutations in renal cell carcinoma (RCC) is associated with a novel subtype of renal cancer, with distinct molecular characteristics compared to VHL mutations. These findings support the emergence of a new molecularly defined tumor entity.
Article
Genetics & Heredity
Michael Prummer, Anne Bertolini, Lars Bosshard, Florian Barkmann, Josephine Yates, Valentina Boeva, Daniel Stekhoven, Franziska Singer
Summary: scROSHI is a method for single-cell analysis that utilizes previously obtained cell type-specific gene lists and does not require training or annotated data. By respecting the hierarchical nature of cell type relationships and assigning cells consecutively to more specialized identities, it achieves excellent prediction performance.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Review
Oncology
Paulino Tallon de Lara, Hector Castanon, Michelle Sterpi, Maries van den Broek
Summary: This article reviews the role and mechanisms of CD8(+) T cells in metastatic cancers, including their functions in controlling metastatic lesions, metastatic dormancy, metastatic clonal evolution, and their clinical implications.
