Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells

Publication date: 3 December 2019Source: Cell Reports, Volume 29, Issue 10Author(s): Assaf Magen, Jia Nie, Thomas Ciucci, Samira Tamoutounour, Yongmei Zhao, Monika Mehta, Bao Tran, Dorian B. McGavern, Sridhar Hannenhalli, Rémy BosselutSummaryMost current tumor immunotherapy strategies leverage cytotoxic CD8+ T cells. Despite evidence for clinical potential of CD4+ tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific CD4+ TILs and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identify TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy. Our study provides a proof-of-concept methodology to characterize tumor-specific CD4+ T cell effector programs. Targeting these programs should help improve immunotherapy strategies.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

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Publication date: Available online 17 January 2020Source: European UrologyAuthor(s): Andrea Necchi, Russell Madison, Daniele Raggi, Joseph M. Jacob, Gennady Bratslavsky, Oleg Shapiro, Julia A. Elvin, Jo-Anne Vergilio, Jonathan K. Killian, Nhu Ngo, Shakti Ramkissoon, Eric Severson, Amanda C. Hemmerich, Richard Huang, Siraj M. Ali, Jon H. Chung, Prasanth Reddy, Vincent A. Miller, Alexa B. Schrock, Laurie M. GayAbstractBackgroundIn patients with rare histologies of bladder cancer, including adenocarcinoma of the bladder (ACB) and squamous-cell carcinoma (SCC), there are limited standard therapy options, defining an unmet medi...
Source: European Urology - Category: Urology & Nephrology Source Type: research
AbstractCancer immunotherapies are promising treatments for many forms of cancer. Nevertheless, the response rates to, e.g., immune checkpoint inhibitors (ICI), are still in low double-digit percentage. This calls for further therapy optimization that should take into account combination of immunotherapies with classical tumor therapies such as radiotherapy. By designing multimodal approaches, immune modulatory properties of certain radiation schemes, additional immune modulation by immunotherapy with ICI and hyperthermia, as well as patient stratification based on genetic and immune constitutions have to be considered. In...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Conclusion: ATLIII has shown significant efficacy to inhibit IFN-γ-triggered Jak3/Stat3 pathway-dependent IDO activation, and do so through a direct binding to Jak3 protein. This study elucidated a new mechanism for the anticancer effect of ATLIII, which may provide a feasible target for the clinical immunotherapy of malignant tumors.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
That cancer mortality is declining at a time in which the aged segment of the population is growing, and ever more people are overweight and obese, is a testament to (a) improved prevention (largely fewer people smoking, which has a sizable impact on lung cancer incidence and severity) and (b) the ever increasing efficacy of modern cancer treatments, particularly immunotherapies. These newer cancer therapies are still in the comparatively early stages of evolution as a technology platform, and we should expect these gains to continue. The immunotherapies of the 2030s will be very impressive in comparison to those deployed ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Immune checkpoint inhibitor (ICI) has been proven to be a major breakthrough in patients with advanced non-small cell lung cancer. Up to now, neoadjuvant therapy using ICI are rare. However, in the context of cancer immunotherapy, neoadjuvant treatment may offer an extra advantage. In this review, we will disscuss the existing preclinical data and emerging clinical findings in the neoadjuvant setting and its potential mechanism of action. We will also highlight the potential damage and the questions that are required to be answered. 
 DOI: 10.3779/j.issn.1009-3419.2020.01.09
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
Here, a model-free controller for cancer treatment is presented. The treatment objective is to find a proper drug dosage that can reduce the population of tumour cells. Recently, some solutions have been proposed according to the control theory. In these approaches, based on the mathematical description of the number of effector cells, tumour cells, and concentration of the interleukin-2 (IL-2), a non-linear controller is designed. Here, based on the back-stepping design procedure and function approximation property of Legendre polynomials, a novel controller for MIMO cancer immunotherapy is presented. In fact, Legendre po...
Source: IET Systems Biology - Category: Biology Source Type: research
While rodent cancer models are essential for early proof-of-concept and mechanistic studies for immune therapies, these models have limitations with regards to predicting the ultimate effectiveness of new immunotherapies in humans. As a unique spontaneous, large animal model of cancer, the value of conducting studies in pet dogs with cancer has been increasingly recognized by the research community. This review will therefore summarize key aspects of the dog cancer immunotherapy model and the role that these studies may play in the overall immunotherapy drug research effort. We will focus on cancer types and settings in wh...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Gut microbiota refers to the diverse community of more than 100 trillion microorganisms residing in our intestines. It is now known that any shift in the composition of gut microbiota from that present during the healthy state in an individual is associated with predisposition to multiple pathological conditions, such as diabetes, autoimmunity, and even cancer. Currently, therapies targeting programmed cell death protein 1/programmed cell death 1 ligand 1 or cytotoxic T-lymphocyte antigen-4 are the focus of cancer immunotherapy and are widely applied in clinical treatment of various tumors. Owing to relatively low overall ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: Our findings demonstrate that tumor-infiltrating NKG2A+ CD8+ T cells form the predominant subset of NKG2A+ cells in human lung cancer and suggest that targeting NKG2A+ CD8+ T cells is a promising approach for future anti-lung cancer immunotherapy.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
NK cells play an important role in the innate defenses against tumor growth and metastases. Human NK cell activation and function are regulated by an array of HLA class I-specific inhibitory receptors and activating receptors recognizing ligands expressed de novo on tumor or virus-infected cells. NK cells have been exploited in immunotherapy of cancer, including: (1) the in vivo infusion of IL-2 or IL-15, cytokines inducing activation and proliferation of NK cells that are frequently impaired in cancer patients. Nonetheless, the significant toxicity experienced, primarily with IL-2, limited their use except for combination...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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