keyword
https://read.qxmd.com/read/38489268/ddx3-regulates-cancer-immune-surveillance-via-3-utr-mediated-cell-surface-expression-of-pd-l1
#1
JOURNAL ARTICLE
Hung-Hsi Chen, Hsin-I Yu, Jason Jie-Sheng Chang, Chia-Wei Li, Muh-Hwa Yang, Mien-Chie Hung, Woan-Yuh Tarn
Programmed death-1 (PD-1)/PD ligand-1 (PD-L1)-mediated immune escape contributes to cancer development and has been targeted as an anti-cancer strategy. Here, we show that inhibition of the RNA helicase DDX3 increased CD8+ T cell infiltration in syngeneic oral squamous cell carcinoma tumors. DDX3 knockdown compromised interferon-γ-induced PD-L1 expression and, in particular, reduced the level of cell-surface PD-L1. DDX3 promoted surface PD-L1 expression by recruiting the adaptor protein 2 (AP2) complex to the 3' UTR of PD-L1 mRNA...
March 13, 2024: Cell Reports
https://read.qxmd.com/read/38489142/non-tumor-related-prognostic-factors-for-immunotherapy-chemotherapy-or-immunotherapy-alone-as-first-line-in-advanced-non-small-cell-lung-cancer-nsclc
#2
JOURNAL ARTICLE
Ziwei Guo, Xing Wei, Chuanhao Tang, Jun Liang
Besides programmed death ligand 1 (PD-L1) expression, rapid, cost-effective and validated scores or models are critical for the prognosis and prediction of patients received immune checkpoint inhibitors (ICIs). In this retrospective study, 182 patients with NSCLC receiving ICIs from 2015 to 2022 were divided 1:1 into a training cohort and a validation cohort. We identified a score established by three factors and analyzed the prognostic implications by Kaplan-Meier approach (Log rank test) and time-dependent receiver operating characteristic (ROC) analyses...
March 15, 2024: Clinical and Experimental Medicine
https://read.qxmd.com/read/38485188/efficacy-safety-and-biomarker-analyses-of-bintrafusp-alfa-a-bifunctional-fusion-protein-targeting-tgf-%C3%AE-and-pd-l1-in-patients-with-advanced-non-small-cell-lung-cancer
#3
JOURNAL ARTICLE
Arun Rajan, Houssein Abdul Sater, Osama Rahma, Richy Agajanian, Wiem Lassoued, Jennifer L Marté, Yo-Ting Tsai, Renee N Donahue, Elizabeth Lamping, Shania Bailey, Andrew Weisman, Beatriz Walter-Rodriguez, Rena Ito, Yulia Vugmeyster, Masashi Sato, Andreas Machl, Jeffrey Schlom, James L Gulley
BACKGROUND: Bintrafusp alfa, a first-in-class bifunctional fusion protein targeting transforming growth factor-β (TGF-β) and programmed cell death ligand 1, has demonstrated encouraging efficacy as second-line treatment in patients with non-small cell lung cancer (NSCLC) in a dose expansion cohort of the phase 1, open-label clinical trial (NCT02517398). Here, we report the safety, efficacy, and biomarker analysis of bintrafusp alfa in a second expansion cohort of the same trial (biomarker cohort)...
March 13, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38485184/phase-ii-study-of-nivolumab-in-patients-with-genetic-alterations-in-dna-damage-repair-and-response-who-progressed-after-standard-treatment-for-metastatic-solid-cancers-km-06
#4
JOURNAL ARTICLE
Ju Won Kim, Hyo Jin Lee, Ji Yoon Lee, Sook Ryun Park, Yu Jung Kim, In Gyu Hwang, Woo Kyun Bae, Jae Ho Byun, Jung Sun Kim, Eun Joo Kang, Jeeyun Lee, Sang Joon Shin, Won Jin Chang, Eun-Ok Kim, Jason K Sa, Kyong Hwa Park
BACKGROUND: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies...
March 13, 2024: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/38482435/study-on-the-effect-of-different-durations-of-decalcification-and-depigmentation-on-programmed-death-ligand-1-immunohistochemical-staining
#5
JOURNAL ARTICLE
Chengmin Zhou, Jun Hou, Hao Dong, Yang Liu, Yehan Zhou
BACKGROUND: Programmed death ligand 1 (PD-L1) score is an important companion diagnosis to predict the response to immunotherapy. Immunohistochemistry can accurately assess the expression of PD-L1 in routine paraffin-embedded tissue. However, whether decalcified or depigmented tissue is still accurate and can be used as a companion diagnosis is controversial. This study attempts to resolve this controversy by analyzing the effects of decalcification and depigmentation at different times on PD-L1 expression...
February 29, 2024: Translational Cancer Research
https://read.qxmd.com/read/38482411/pd-1-induced-encephalopathy-a-report-of-2-cases-on-neurological-toxicities-with-immune-checkpoint-inhibitors
#6
Xingrui Chen, Minting Ye, Ruyu Ai, Changguo Shan, Minyao Lai, Weiping Hong, Yanying Yang, Hui Wang, Juan Li, Junjie Zhen, Jiangfen Zhou, Qingjun Hu, Shaoqun Li, Antonio Rossi, Toyoaki Hida, Rafael Rosell, Shuisheng Zhong, Linbo Cai
BACKGROUND: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support...
February 29, 2024: Translational Cancer Research
https://read.qxmd.com/read/38481857/a-narrative-review-of-management-of-muscle-invasive-bladder-cancer-perioperative-period-will-continuous-and-combined-treatment-be-the-new-trend
#7
REVIEW
Tianhang Lan, Shengming Ran, Mingchao Gao, Wenjie Li, Wang He
BACKGROUND AND OBJECTIVE: With the emergence of immunotherapy and targeted therapies, there are more options for the perioperative period management of muscle-invasive bladder cancer (MIBC), and various types of clinical studies are emerging, leading to the need to explore ways to choose the optimal treatment modality. This review aims to synthesize past and present treatment modalities and to explore future trends in the perioperative period cares of MIBC for the benefit of clinical practitioners...
February 29, 2024: Translational Andrology and Urology
https://read.qxmd.com/read/38478111/a-comprehensive-multi-omics-analysis-identifies-a-robust-scoring-system-for-cancer-associated-fibroblasts-and-intervention-targets-in-colorectal-cancer
#8
JOURNAL ARTICLE
Feng Wang, Zhenlin Li, Tianlei Xu, Qian Zhang, Tianyi Ma, Sijia Li, Xiaohui Wang
BACKGROUND: Cancer-associated fibroblasts (CAF) play a critical role in promoting tumor growth, metastasis, and immune evasion. While numerous studies have investigated CAF, there remains a paucity of research on their clinical application in colorectal cancer (CRC). METHODS: In this study, we collected differentially expressed genes between CAF and normal fibroblasts (NF) from previous CRC studies, and utilized machine learning analysis to differentiate two distinct subtypes of CAF in CRC...
March 13, 2024: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/38476610/prognostic-biomarker-cpeb3-and-its-associations-with-immune-infiltration-in-clear-cell-renal-cell-carcinoma
#9
JOURNAL ARTICLE
Hualan Hong, Xi Shi, Wenyong Ou, Pengju Ou
The role and underlying mechanism of cytoplasmic polyadenylation element binding protein 3 (CPEB3) in clear cell renal cell carcinoma [ccRCC progression remain poorly characterized. The present study was designed to evaluate the role of CPEB3 in ccRCC and its clinical associations. The overall response rate of first-line therapies (ICIs combined with VEGFR-TKIs or ICI combination) for ccRCC] is 42.0-59.3%, so a number of patients with ccRCC do not benefit from these therapies. To avoid immunosurveillance and immune killing, tumor cells decrease immunogenicity and recruit immunosuppressive cells such as regulatory T cells (Tregs)...
April 2024: Biomedical Reports
https://read.qxmd.com/read/38472118/targeted-degradation-of-cell-surface-proteins-via-chaperone-mediated-autophagy-by-using-peptide-conjugated-antibodies
#10
JOURNAL ARTICLE
Jinning Shao, Xuefen Lin, Haoting Wang, Chuhan Zhao, Shao Q Yao, Jingyan Ge, Su Zeng, Linghui Qian
Cell-surface proteins are important drug targets but historically have posed big challenges for the complete elimination of their functions. Herein, we report antibody-peptide conjugates (Ab-CMAs) in which a peptide targeting chaperone-mediated autophagy (CMA) was conjugated with commercially available monoclonal antibodies for specific cell-surface protein degradation by taking advantage of lysosomal degradation pathways. Unique features of Ab-CMAs including cell-surface receptor-/E3 ligase-independent degradation, feasibility towards different cell-surface proteins (e...
March 12, 2024: Angewandte Chemie
https://read.qxmd.com/read/38464519/prognostic-impact-of-clinical-factors-for-immune-checkpoint-inhibitor-with-or-without-chemotherapy-in-older-patients-with-non-small-cell-lung-cancer-and-pd-l1-tps-%C3%A2-50
#11
JOURNAL ARTICLE
Shota Takei, Hayato Kawachi, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Keiko Tanimura, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Nobuyo Tamiya, Yuki Katayama, Naoya Nishioka, Kenji Morimoto, Masahiro Iwasaku, Shinsaku Tokuda, Takashi Kijima, Koichi Takayama
INTRODUCTION: The proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38456253/association-of-pd-l1-expression-with-driver-gene-mutations-and-clinicopathological-characteristics-in-non-small-cell-lung-cancer-a-real-world-study-of-10%C3%A2-441-patients
#12
JOURNAL ARTICLE
Gonzalo Ruiz, Diego Enrico, Yamil D Mahmoud, Alan Ruiz, María Florencia Cantarella, Laura Leguina, Mariana Barberis, Asunción Beña, Esteban Brest, Solange Starapoli, Andrea Mendoza Bertelli, Florencia Tsou, Carmen Pupareli, María Pía Coppola, Alejandra Scocimarro, Susana Sena, Patricio Levit, Aldo Perfetti, Enrique Aman, María Romina Girotti, Oscar Arrieta, Claudio Martín, Rubén Salanova
BACKGROUND: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. METHODS: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples...
March 8, 2024: Thoracic Cancer
https://read.qxmd.com/read/38455414/clinical-implications-of-pd-l1-expression-and-pathway-related-molecular-subtypes-in-advanced-asian-colorectal-cancer-patients
#13
JOURNAL ARTICLE
Qingqing Qiu, Dan Tan, Qiaofeng Chen, Ru Zhou, Xiaokai Zhao, Wei Wen, Pengmin Yang, Jieyi Li, Ziying Gong, Daoyun Zhang, Mingliang Wang
The expression level of PD-L1 does not accurately predict the prognosis of advanced colorectal cancer (CRC) patients, but it still reflects the tumor microenvironment to some extent. By stratifying PD-L1 status, gene subtypes in PD-L1 positivity-related pathological pathways were analyzed for their relationship to MSI or TMB to provide more individualized treatment options for CRCs. A total of 752 advanced CRCs were included, and their genomic variance was measured by a targeted next generation sequencing panel in this study...
2024: American Journal of Cancer Research
https://read.qxmd.com/read/38455365/clinicopathological-significance-and-immunotherapeutic-outcome-of-claudin-18-2-expression-in-advanced-gastric-cancer-a-retrospective-study
#14
JOURNAL ARTICLE
Changsong Qi, Xiaoyi Chong, Ting Zhou, Mingyang Ma, Jifang Gong, Miao Zhang, Jian Li, Jun Xiao, Xiaohui Peng, Zhen Liu, Zonghai Li, Lin Shen, Xiaotian Zhang
OBJECTIVE: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive (CLDN18.2-positive) gastric cancer (GC) vary in different clinical studies, making it difficult to optimize anti-CLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC. METHODS: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01 clinical trials were included in the analysis...
February 29, 2024: Chinese Journal of Cancer Research
https://read.qxmd.com/read/38455346/perspectives-on-surgical-treatment-for-thymic-epithelial-tumors-a-narrative-review
#15
REVIEW
Yusuke Nabe, Masaaki Inoue, Junichi Yoshida
BACKGROUND AND OBJECTIVE: Thymic epithelial tumors are relatively rare; thus, mostly retrospective studies and a few prospective randomized controlled trials have been conducted on the treatment and the biomarkers, with no standard therapy established. Indications for extended thymectomy, robot-assisted thoracic surgery, and multidisciplinary treatment are controversial. Here, we considered the prospects of surgical treatment and the possibility of immune checkpoint inhibitor (ICI) treatment for thymic epithelial tumors...
February 29, 2024: Gland Surgery
https://read.qxmd.com/read/38451524/neoadjuvant-adjuvant-vs-neoadjuvant-only-pd-1-and-pd-l1-inhibitors-for-patients-with-resectable-nsclc-an-indirect-meta-analysis
#16
JOURNAL ARTICLE
Yixin Zhou, Anlin Li, Hui Yu, Yuhong Wang, Xuanye Zhang, Huijuan Qiu, Wei Du, Linfeng Luo, Sha Fu, Li Zhang, Shaodong Hong
IMPORTANCE: Neoadjuvant therapy combining programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors with platinum-based chemotherapy has demonstrated significant improvement in pathologic response and survival rates among patients with resectable non-small cell lung cancer (NSCLC). However, it remains controversial whether PD-1 blockade therapy given before and after surgery (neoadjuvant-adjuvant treatment) is associated with better outcomes than when given only before surgery (neoadjuvant-only treatment)...
March 4, 2024: JAMA Network Open
https://read.qxmd.com/read/38446479/significance-of-pd-l1-in-metastatic-urothelial-carcinoma-treated-with-immune-checkpoint-inhibitors-a-systematic-review-and-meta-analysis
#17
JOURNAL ARTICLE
Brigida Anna Maiorano, Massimo Di Maio, Linda Cerbone, Evaristo Maiello, Giuseppe Procopio, Giandomenico Roviello
IMPORTANCE: Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1) with response and survival in patients treated with ICIs is still controversial. OBJECTIVES: To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs. DATA SOURCES: PubMed, Embase, American Society of Clinical Oncology and European Society for Medical Oncology Meeting Libraries, and Web of Science were searched up to December 10, 2023...
March 4, 2024: JAMA Network Open
https://read.qxmd.com/read/38445936/prognostic-implications-of-tumor-infiltrating-lymphocytes-within-the-tumor-microenvironment-in-gastric-cancer
#18
JOURNAL ARTICLE
Marina Alessandra Pereira, Marcus Fernando Kodama Pertille Ramos, Leonardo Cardili, Rafael Dyer Rodrigues de Moraes, André Roncon Dias, Daniel Jose Szor, Bruno Zilberstein, Venancio Avancini Ferreira Alves, Evandro Sobroza de Mello, Ulysses Ribeiro
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) play a regulatory role in the tumor-associated immune response and are important in the prognosis and treatment response of several cancers. However, because of its heterogeneity, the prognostic value of TILs in gastric cancer (GC) is still controversial. Thus, this study aimed to investigate the association between the density of TILs and patients' outcomes in GC. METHODS: Patients with gastric adenocarcinoma who underwent curative intent gastrectomy were retrospectively investigated...
February 2024: Journal of Gastrointestinal Surgery
https://read.qxmd.com/read/38445519/tertiary-lymphoid-structure-associated-b-cells-enhance-cxcl13-cd103-cd8-tissue-resident-memory-t-cell-response-to-programmed-cell-death-protein-1-blockade-in-cancer-immunotherapy
#19
JOURNAL ARTICLE
Chupeng Hu, Wenhua You, Deyuan Kong, Yedi Huang, JinYing Lu, Mengya Zhao, Yu Jin, Rui Peng, Dong Hua, Dong-Ming Kuang, Yun Chen
BACKGROUND & AIMS: Although the presence of tertiary lymphoid structures (TLS) correlates with positive responses to immunotherapy in many solid malignancies, the mechanism by which TLS enhances antitumor immunity is not well understood. The present study aimed to investigate the underlying cross talk circuits between B cells and tissue-resident memory T (Trm) cells within the TLS and to understand their role in the context of immunotherapy. METHODS: Immunostaining and H&E staining of TLS and chemokine (C-X-C motif) ligand 13 (CXCL13)+ cluster of differentiation (CD)103+ CD8+ Trm cells were performed on tumor sections from patients with gastric cancer (GC)...
October 29, 2023: Gastroenterology
https://read.qxmd.com/read/38442487/development-and-in-vivo-evaluation-of-small-molecule-ligands-for-positron-emission-tomography-of-immune-checkpoint-modulation-targeting-programmed-cell-death-1-ligand-1
#20
JOURNAL ARTICLE
Karsten Bamminger, Verena Pichler, Chrysoula Vraka, Tanja Limberger, Boryana Moneva, Katharina Pallitsch, Barbara Lieder, Anna Sophia Zacher, Stefanie Ponti, Katarína Benčurová, Jiaye Yang, Sandra Högler, Petra Kodajova, Lukas Kenner, Marcus Hacker, Wolfgang Wadsak
A substantial portion of patients do not benefit from programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) checkpoint inhibition therapies, necessitating a deeper understanding of predictive biomarkers. Immunohistochemistry (IHC) has played a pivotal role in assessing PD-L1 expression, but small-molecule positron emission tomography (PET) tracers could offer a promising avenue to address IHC-associated limitations, i.e., invasiveness and PD-L1 expression heterogeneity. PET tracers would allow for improved quantification of PD-L1 through noninvasive whole-body imaging, thereby enhancing patient stratification...
March 5, 2024: Journal of Medicinal Chemistry
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