TLR9 acts as a sensor for tumor-released DNA to modulate anti-tumor immunity after chemotherapy

AbstractThe tumor microenvironment exists in a state of dynamic equilibrium, in which a balance of agonist and antagonist signals govern the anti-tumor immune responses. Previous studies have shown that chemotherapy could shift this balance in favor of agonistic signals for the anti-tumor immune responses mounted by CD8+ cytotoxic T lymphocytes (CTL), providing sufficiently high antigen density within the tumor. We undertook the current study to characterize the anti-tumor immune response following chemotherapy and its underlying mechanisms. We show that this ‘adjuvant effect’ of chemotherapy is, at least partially, mediated by the release of tumor DNA and acts through the Toll-like receptor 9 (TLR9) pathway. We found that tumor-released DNA causes accumulation, antigen uptake, and maturation of dendritic cells (DCs) in the tumor in a TLR9-dependent manner. These DCs subsequently migrate into the draining lymph nodes and prime tumor-specific CTLs. Our study provides novel insights to the molecular and cellular mechanisms by which chemotherapy converts the tumor microenvironment into a site permissive for the activation of a potent tumor-specifi c adaptive immune response.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research

Related Links:

Authors: Tribius S, Würdemann N, Laban S, Hoffmann TK, Sharma SJ, Klussmann JP Abstract At this year's Annual Meeting of the American Society for Clinical Oncology (ASCO), the keyword search "HPV-associated head and neck cancer" resulted in 920 hits-74% of the hits on human papillomavirus (HPV). This underlines the relevance of the topic. The spectrum ranged from validation and separation of the prognostic groups of patients with HPV-associated oropharyngeal carcinoma (OPSCC) according to TNM 8, to the characterization of new tumor markers and tumor mutational burden for possible de-escalation s...
Source: HNO - Category: ENT & OMF Tags: HNO Source Type: research
AbstractPurpose of ReviewImmune checkpoint blockade (ICB) has changed the clinical course of multiple cancer types and durable responses have now been observed in breast cancer (BC) patients. Most data suggest that, compared to other subtypes, triple-negative BC (TNBC) patients are more responsive to ICB, and anti-PD-L1 therapy is now approved in PD-L1+ metastatic TNBC, in combination with chemotherapy.Recent FindingsNearly 40% of PD-L1+ TNBC patients did not respond to this combination. Thus, additional biomarkers appear to be necessary to more precisely identify potential responders. A comprehensive analysis of the breas...
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research
ConclusionsThe updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes.Patient summaryIn the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other pre...
Source: European Urology - Category: Urology & Nephrology Source Type: research
Conditions:   Pancreatic Adenocarcinoma;   Pancreatic Cancer Intervention:   Biological: Autologous DC vaccine Sponsors:   Baylor College of Medicine;   Cancer Cures for Kids Not yet recruiting
Source: - Category: Research Source Type: clinical trials
This study evaluated the therapeutic and survival disparities among patients with advanced MMel based on hospital volume using the National Cancer Database (NCDB). METHODS: A retrospective analysis using regression models and Kaplan-Meier estimates was performed from the data obtained from the NCDB on patients with MMel diagnosed in 2004 through 2015. RESULTS: A total of 40,676 patients with MMel were treated at 1,260 facilities. Multivariable analysis showed that facility volume was an independent predictor of overall survival (P
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
Authors: Unni P, Seshaiyer P Abstract Over the last few decades, there have been significant developments in theoretical, experimental, and clinical approaches to understand the dynamics of cancer cells and their interactions with the immune system. These have led to the development of important methods for cancer therapy including virotherapy, immunotherapy, chemotherapy, targeted drug therapy, and many others. Along with this, there have also been some developments on analytical and computational models to help provide insights into clinical observations. This work develops a new mathematical model that combines ...
Source: Computational and Mathematical Methods in Medicine - Category: Statistics Tags: Comput Math Methods Med Source Type: research
This article summarizes the established and new options in additive systemic treatment and presents the current state of treatment. PMID: 31705281 [PubMed - as supplied by publisher]
Source: Der Chirurg - Category: Surgery Authors: Tags: Chirurg Source Type: research
Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: November 2019Source: Journal of Geriatric Oncology, Volume 10, Issue 6, Supplement 1Author(s): M.L. Wong, A.K. Smith, C. Miaskowski, V. Musinipally, H.J. Cohen, V. Lam, M. Mazor, C.J. Ursem, K. Loh, J.A. Cohen, D. Shumay, A.O. Levin, N. Dixit, J. Grandi, L.C. Walter
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
Ferumoxytol capped antiprogrammed cell death ‐ligand 1 (PD‐L1) antibodies (aPD‐L1) loaded ultralarge pore mesoporous silica nanoparticles are delivered with image guidance after cabazitaxel (Cbz) chemotherapy for the treatment of prostate cancer. A single session of sequential magnetic resonance image guided chemo‐immunotherapy effecti vely activates T cell infiltration, insisting tumor specific adaptive immunity and tumor rejection superior to systemic aPD‐L1 treatment after Cbz of the same dose. AbstractHerein, ferumoxytol (Fer) capped antiprogrammed cell death ‐ligand 1 (PD‐L1) antibodies (aPD‐L1) loaded...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
More News: Cancer | Cancer & Oncology | Chemotherapy | Immunotherapy | Study