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JOURNAL ARTICLE
Qingyang Lei, Shanshan Zhen, Lei Zhang, Qitai Zhao, Li Yang, Yi Zhang
Tumor-associated macrophages (TAMs) are abundant in tumors and interact with tumor cells, leading to the formation of an immunosuppressive microenvironment and tumor progression. Although many studies have explored the mechanisms underlying TAM polarization and its immunosuppressive functions, understanding of its progression remains limited. TAMs promote tumor progression by secreting cytokines, which subsequently recruit immunosuppressive cells to suppress the antitumor immunity. In this study, we established an in vitro model of macrophage and non-small cell lung cancer (NSCLC) cell co-culture to explore the mechanisms of cell-cell crosstalk...
April 20, 2024: Cancer Immunology, Immunotherapy: CII
#2
JOURNAL ARTICLE
Jing Xu, Wen Zhang, Jinlian Tong, Caixia Liu, Qiaohui Zhang, Liren Cao, Jiangyong Yu, Aiping Zhou, Jie Ma
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge worldwide. Here, we introduced a phase I trial of autologous RAK cell therapy in patients with mRCC whose cancers progressed after prior systemic therapy. Although RAK cells have been used in clinic for many years, there has been no dose-escalation study to demonstrate its safety and efficacy. METHODS: We conducted a phase I trial with a 3 + 3 dose-escalation design to investigate the dose-related safety and efficacy of RAK cells in patients with mRCC whose cancers have failed to response to systemic therapy (ChiCTR1900021334)...
April 20, 2024: Cancer Immunology, Immunotherapy: CII
#3
Ke Li, Jing Xu, Jing Wang, Chong Lu, Yilin Dai, Qing Dai, Wang Zhang, Congjian Xu, Shu Wu, Yu Kang
No abstract text is available yet for this article.
April 18, 2024: Cancer Immunology, Immunotherapy: CII
#4
JOURNAL ARTICLE
Francesco Massari, Matteo Santoni, Hideki Takeshita, Yohei Okada, Jose Carlos Tapia, Umberto Basso, Marco Maruzzo, Sarah Scagliarini, Thomas Büttner, Giuseppe Fornarini, Zin W Myint, Luca Galli, Vinicius Carrera Souza, Renate Pichler, Ugo De Giorgi, Nathalia Gandur, Elaine T Lam, Danielle Gilbert, Lazar Popovic, Enrique Grande, Giulia Mammone, Rossana Berardi, Simon J Crabb, Robert Kemp, Javier Molina-Cerrillo, Marcelo Freitas, Murilo Luz, Roberto Iacovelli, Fabio Calabrò, Deniz Tural, Francesco Atzori, Zsófia Küronya, Rita Chiari, Saul Campos, Orazio Caffo, André P Fay, Jakub Kucharz, Paolo Andrea Zucali, José Augusto Rinck, Annalisa Zeppellini, Diogo Assed Bastos, Gaetano Aurilio, Augusto Mota, Karine Trindade, Cinzia Ortega, Juan Pablo Sade, Mimma Rizzo, Ondřej Fiala, Nuno Vau, Patrizia Giannatempo, Allan Barillas, Fernando Sabino M Monteiro, Breno Dauster, Alessia Mennitto, Lucas Nogueira, Roni de Carvalho Fernandes, Emmanuel Seront, Luís Garcia Aceituno, Francesco Grillone, Hernan Javier Cutuli, Mauricio Fernandez, Maria Bassanelli, Ray Manneh Kopp, Giandomenico Roviello, Halima Abahssain, Giuseppe Procopio, Michele Milella, Jindrich Kopecky, Angelo Martignetti, Carlo Messina, Manuel Caitano, Eva Inman, Ravindran Kanesvaran, Daniel Herchhorn, Daniele Santini, Aristotelis Bamias, Renato Bisonni, Alessandra Mosca, Franco Morelli, Fernando Maluf, Andrey Soares, Fernando Nunes, Alvaro Pinto, Anca Zgura, Lorena Incorvaia, Jawaher Ansari, Ignacio Ortego Zabalza, Johannes Landmesser, Alessandro Rizzo, Veronica Mollica, Andrea Marchetti, Matteo Rosellini, Giulia Sorgentoni, Nicola Battelli, Sebastiano Buti, Camillo Porta, Joaquim Bellmunt
BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries...
April 18, 2024: Cancer Immunology, Immunotherapy: CII
#5
JOURNAL ARTICLE
Junseok Lee, Keon-Il Im, Sojin Gil, Hyemin Na, Gi-June Min, Nayoun Kim, Seok-Goo Cho
Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
#6
JOURNAL ARTICLE
Sophia Stock, Luisa Fertig, Adrian Gottschlich, Janina Dörr, Florian Märkl, Lina Majed, Vivien D Menkhoff, Ruth Grünmeier, Kai Rejeski, David M Cordas Dos Santos, Sebastian Theurich, Michael von Bergwelt-Baildon, Stefan Endres, Marion Subklewe, Sebastian Kobold
In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
#7
JOURNAL ARTICLE
Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
#8
JOURNAL ARTICLE
Sha Ma, Ying Wang, Kunming Qi, Wenyi Lu, Yuekun Qi, Jiang Cao, Mingshan Niu, Depeng Li, Wei Sang, Zhiling Yan, Feng Zhu, Hai Cheng, Zhenyu Li, Mingfeng Zhao, Kailin Xu
Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We present a retrospective study of 67 patients with R/R B-ALL who received anti-CD19 CAR T-cell therapy, 41 (61.2%) patients received G-CSF (G-CSF group), while 26 (38.8%) did not (non-G-CSF group). Patients had similar duration of grade 3-4 neutropenia between the two groups...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
#9
JOURNAL ARTICLE
Lanqun Qin, Guiying Zhang, Yirong Wu, Yueling Yang, Zhengyun Zou
As one of the scheduled immunization vaccines worldwide, virtually all individuals have been vaccinated with BCG vaccine. In order to verify the hypothesis that delivering BCG high-affinity peptides to tumor areas could activate the existing BCG memory T cells to attack tumor, we firstly predicted the HLA-A*0201 high-affinity peptides of BCG Ag85A protein (KLIANNTRV, GLPVEYLQV), and then, A375 melanoma cells and HLA-A*0201 PBMCs (from PPD-positive adults) were added to co-incubated with the predicted peptides in vitro...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
#10
JOURNAL ARTICLE
Nithidol Sakunrangsit, Nattarika Khuisangeam, Thananya Inthanachai, Varalee Yodsurang, Pasrawin Taechawattananant, Koramit Suppipat, Supannikar Tawinwung
CAR-T-cell therapy has shown promise in treating hematological malignancies but faces challenges in treating solid tumors due to impaired T-cell function in the tumor microenvironment. To provide optimal T-cell activation, we developed a B7 homolog 3 protein (B7H3)-targeting CAR construct consisting of three activation signals: CD3ζ (signal 1), 41BB (signal 2), and the interleukin 7 receptor alpha (IL7Rα) cytoplasmic domain (signal 3). We generated B7H3 CAR-T cells with different lengths of the IL7Rα cytoplasmic domain, including the full length (IL7R-L), intermediate length (IL7R-M), and short length (IL7R-S) domains, and evaluated their functionality in vitro and in vivo...
April 15, 2024: Cancer Immunology, Immunotherapy: CII
#11
JOURNAL ARTICLE
Ling Yi, Ziwei Xu, Tianyu Ma, Chong Wang, Panjian Wei, Bo Xiao, Hongtao Zhang, Nanying Che, Zhidong Liu, Yi Han
PURPOSE: Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. METHODS: Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry...
April 15, 2024: Cancer Immunology, Immunotherapy: CII
#12
JOURNAL ARTICLE
Jessica Wedig, Shrina Jasani, Debasmita Mukherjee, Hannah Lathrop, Priya Matreja, Timothy Pfau, Liliana D'Alesio, Abigail Guenther, Lexie Fenn, Morgan Kaiser, Molly A Torok, Jake McGue, Gina M Sizemore, Anne M Noonan, Mary E Dillhoff, Bradley W Blaser, Timothy L Frankel, Stacey Culp, Phil A Hart, Zobeida Cruz-Monserrate, Thomas A Mace
Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor survival is attributed, in part, to limited and ineffective treatments for patients with metastatic disease, highlighting a need to identify molecular drivers of pancreatic cancer to target for more effective treatment. CD200 is a glycoprotein that interacts with the receptor CD200R and elicits an immunosuppressive response. Overexpression of CD200 has been associated with differential outcomes, depending on the tumor type...
April 15, 2024: Cancer Immunology, Immunotherapy: CII
#13
JOURNAL ARTICLE
Maosheng Cheng, Jianqi Xiong, Qianwen Liu, Caihua Zhang, Kang Li, Xinyuan Wang, Shuang Chen
Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues...
April 15, 2024: Cancer Immunology, Immunotherapy: CII
#14
JOURNAL ARTICLE
Ziyang Xu, Wenbin Jiang, Li Liu, Youqi Qiu, Jiahao Wang, Siyuan Dai, Jianming Guo, Jiejie Xu
BACKGROUND: Homologous recombination deficiency (HRD), though largely uncharacterized in clear cell renal cell carcinoma (ccRCC), was found associated with RAD51 loss of expression. PBRM1 is the second most common mutated genes in ccRCC. Here, we introduce a HRD function-based PBRM1-RAD51 ccRCC classification endowed with diverse immune checkpoint blockade (ICB) responses. METHODS: Totally 1542 patients from four independent cohorts were enrolled, including our localized Zhongshan hospital (ZSHS) cohort and Zhongshan hospital metastatic RCC (ZSHS-mRCC) cohort, The Cancer Genome Atlas (TCGA) cohort and CheckMate cohort...
April 12, 2024: Cancer Immunology, Immunotherapy: CII
#15
JOURNAL ARTICLE
Jhen-Yu Chen, Po-Yu Lin, Wei-Ze Hong, Pei-Chen Yang, Shu-Fen Chiang, Hsin-Yu Chang, Tao-Wei Ke, Ji-An Liang, William Tzu-Liang Chen, K S Clifford Chao, Kevin Chih-Yang Huang
Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity...
April 2, 2024: Cancer Immunology, Immunotherapy: CII
#16
REVIEW
Bo Pei, Shixuan Peng, Chuying Huang, Fuxiang Zhou
The advent of tumor immunotherapy in patients has revolutionized the treatment of tumors and significantly improved survival rates for a wide range of tumors. However, the full therapeutic potential of immune checkpoint inhibitors (ICIs) has yet to be realized, as not all patients have a lasting survival benefit from them, and a significant proportion of patients show primary or acquired resistance to immunotherapy. Bifidobacterium is one of the most common probiotics, and its antitumor and immunomodulatory effects have been demonstrated in recent years, but its immunomodulatory effects in tumors, especially on ICIs and in combination, have not been extensively studied in clinical practice, and its effects on the immune system and the mechanisms that modulate immunotherapy are largely unknown...
April 2, 2024: Cancer Immunology, Immunotherapy: CII
#17
JOURNAL ARTICLE
Konstantinos S Papadakos, Gilar Gorji-Bahri, Chrysostomi Gialeli, Charlotta Hedner, Catharina Hagerling, Maria C Svensson, Martin Jeremiasen, David Borg, Richard Fristedt, Karin Jirström, Anna M Blom
BACKGROUND: Cartilage oligomeric matrix protein (COMP) is a novel regulator of the tumor microenvironment. Studies in colon cancer and pancreatobiliary adenocarcinoma have revealed COMP expression to be associated with decreased infiltration of immune cells in the tumor microenvironment. Herein, the expression of COMP was investigated in gastric and esophageal adenocarcinoma with particular reference to its the relationship with the immune microenvironment. METHODS: COMP expression was evaluated in tissue microarrays representing primary tumors from 159 patients with chemo- and radiotherapy naïve esophageal and gastric adenocarcinoma and 67 matched samples of lymph node metastases using immunohistochemistry...
April 2, 2024: Cancer Immunology, Immunotherapy: CII
#18
JOURNAL ARTICLE
Ting Zhou, Husun Qian, Dian Zhang, Wenli Fang, MengLi Yao, He Shi, Tingmei Chen, Chengsen Chai, Bianqin Guo
BACKGROUND: Tumor microenvironment actually reduces antitumor effect against the immune attack by exclusion of CD8+ T cells. Progranulin (PGRN) is a multifunctional growth factor with significant pathological effects in multiple tumors; however, its role in immunity evasion of breast cancer (BCa) is not completely understood. METHODS: We depleted GRN (PGRN gene) genetically in mice or specifically in PY8119 murine BCa cell line, and mouse models of orthotopic or subcutaneous transplantation were used...
March 30, 2024: Cancer Immunology, Immunotherapy: CII
#19
JOURNAL ARTICLE
Zhe Ma, Zhenxing Zhou, Wenwen Duan, Gaofeng Yao, Shimei Sheng, Sidou Zong, Xin Zhang, Changkui Li, Yuanyuan Liu, Fengting Ou, Maha Raja Dahar, Yanshan Huang, Lushan Yu
BACKGROUND: Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy. METHODS: Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18...
March 30, 2024: Cancer Immunology, Immunotherapy: CII
#20
JOURNAL ARTICLE
Zihao Niu, Peng Sun, Mark E Zafereo, Hongliang Liu, Peng Wei, Jia Wu, Neil D Gross, Sanjay Shete, Qingyi Wei, Guibin Zheng, Andy G Sikora, George A Calin, Guojun Li
TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348...
March 30, 2024: Cancer Immunology, Immunotherapy: CII
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