The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy

Programmed death-1 receptor ligand 1 (PD-L1) is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1+ tumors as well as their roles in determining therapeutic efficacies are unknown. Here, we showed, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent the IFN-γ signature and potentially signified proinflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-κB signal elicited by macrophage inflammatory responses generated PD-L1+ cancer cells exhibiting capabilities to aggressively survive, support angiogenesis, and metastasize, whereas STAT1 signal triggered by activated T cells induced PD-L1+ cancer cells susceptive to apoptosis. Importantly, PD-L1+ cancer cells generated by macrophages established great resistance to conventional chemotherapy, cytotoxicity of tumor-specific effector T cells, and therapy of immune-checkpoint blockade. Therapeutic strategy combining immune-checkpoint blockade with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited cancer regression. Our results provide insight into the functional features of PD-L1+ tumors and suggest that strategies to influence functional activities of inflammatory cells may benefit immune-checkpoint blockade therap...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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We agree that the wide variability in postoperative chemotherapy use observed in our study underscores the need to increase guideline-consistent care for nonmuscle invasive bladder cancer. The physician factors we examined – including physician age, years employed at our institution, specialty training in oncology, and experience treating bladder cancer – did not explain the treatment variability. As Dr. Schroeck noted, other physician factors, such as the level of concern about side effects or awareness of and ag reement with guidelines, may be important contributors to treatment variability.
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
The authors report on a retrospective cohort study of 5386 patients diagnosed with nonmuscle-invasive bladder cancer (NMIBC) at Kaiser Permanente Southern California between 2001 and 2015. They find that 41% of patients received any intravesical therapy. Use of postoperative intravesical chemotherapy was rarer (given to 17%), but increased over time. There was substantial variation in use of intravesical therapy across urologists. The variation was greatest for use of postoperative intravesical chemotherapy, with 45% of the observed variation explained by the treating urologist.
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
This study suggests that the DOX-PIO combination could be used in the clinic for osteosarcoma patients who develop DOX-resistance.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 23 August 2019Source: Journal of Cardiology CasesAuthor(s): Shohei Moriyama, Taku Yokoyama, Kei Irie, Mamoru Ito, Kenji Tsuchihashi, Mitsuhiro Fukata, Hitoshi Kusaba, Toru Maruyama, Koichi AkashiAbstractFluorouracil (5-FU), a commonly used anticancer agent, has potent cardiotoxicity that is mediated by vascular endothelial injury and vasospasm. Here, we report a patient demonstrating atrial fibrillation (AF), which was most likely induced by vasospasm mediated by 5-FU.A 69-year-old man presented with dysphagia and was diagnosed with advanced esophageal cancer. Frequent paroxysms of atrial...
Source: Journal of Cardiology Cases - Category: Cardiology Source Type: research
ConclusionsOpioid dependence in the over 65-year old population after lung resection is high but was significantly lower among those who received minimally invasive surgery, in addition to other factors.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Publication date: Available online 20 August 2019Source: Journal of Molecular LiquidsAuthor(s): Sadegh Farhadian, Behzad Shareghi, Farhang Tirgir, Somayeh Reiisi, Neda Gholamian Dehkordi, Lida Momeni, Ehsan HeidariAbstractOver the past decades, anti-cancer drugs consist of cytotoxic drugs have been interested and developed. Despite the great advances in chemotherapy, there is still no certain medical treatment for cancer. During this investigation, a novel 2,5-diketopiperazine derivative 3(R),6(S)-bis (4-hydroxy phenyl)-piperazine-2,5-dione: (BHPPD) was designed, synthesized, and evaluated. The effects on intestinal protea...
Source: Journal of Molecular Liquids - Category: Molecular Biology Source Type: research
Publication date: Available online 15 August 2019Source: Carbohydrate PolymersAuthor(s): Yaping Wang, Junmin Qian, Ming Yang, Weijun Xu, Jinlei Wang, Guanghui Hou, Lijie Ji, Aili SuoAbstractCombination chemotherapy has attracted more and more attention in the field of anticancer treatment. Herein, a synergetic targeted combination chemotherapy of doxorubicin (DOX) and cisplatin in breast cancer was realized by HER2 antibody-decorated nanoparticles assembled from aldehyde hyaluronic acid (AHA) and hydroxyethyl chitosan (HECS). Cisplatin and DOX were successively conjugated onto AHA through chelation and Schiff’s base ...
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
Publication date: Available online 22 August 2019Source: Cancer CellAuthor(s): Salma Parvin, Ariel Ramirez-Labrada, Shlomzion Aumann, XiaoQing Lu, Natalia Weich, Gabriel Santiago, Elena M. Cortizas, Eden Sharabi, Yu Zhang, Isidro Sanchez-Garcia, Andrew J. Gentles, Evan Roberts, Daniel Bilbao-Cortes, Francisco Vega, Jennifer R. Chapman, Ramiro E. Verdun, Izidore S. LossosSummaryDeficiency in DNA double-strand break (DSB) repair mechanisms has been widely exploited for the treatment of different malignances, including homologous recombination (HR)-deficient breast and ovarian cancers. Here we demonstrate that diffuse large B...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
CONCLUSION: The glassy cell carcinoma of the cervix should be considered as an aetiology of bone metastases in young female patients. PMID: 31431320 [PubMed - as supplied by publisher]
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
Patients with metastatic colorectal cancer who have a BRAF mutation have improved survival after treatment with three targeted therapies instead of standard chemotherapy, results from a phase III trial have shown.
Source: Clinical Pharmacist - Category: Drugs & Pharmacology Source Type: research
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