Dendritic Cell Vaccination in Metastatic Melanoma Turns “Non-T Cell Inflamed” Into “T-Cell Inflamed” Tumors

Dendritic cell (DC)-based vaccination effectively induces anti-tumor immunity, although in the majority of cases this does not translate into a durable clinical response. However, DC vaccination is characterized by a robust safety profile, making this treatment a potential candidate for effective combination cancer immunotherapy. To explore this possibility, understanding changes occurring in the tumor microenvironment (TME) upon DC vaccination is required. In this line, quantitative and qualitative changes in tumor-infiltrating T lymphocytes (TILs) induced by vaccination with autologous tumor lysate/homogenate loaded DCs were investigated in a series of 16 patients with metastatic melanoma. Immunohistochemistry for CD4, CD8, Foxp3, Granzyme B (GZMB), PDL1, and HLA class I was performed in tumor biopsies collected before and after DC vaccination. The density of each marker was quantified by automated digital pathology analysis on whole slide images. Co-expression of markers defining functional phenotypes, i.e., Foxp3+ regulatory CD4+ T cells (Treg) and GZMB+ cytotoxic CD8+ T cells, was assessed with sequential immunohistochemistry. A significant increase of CD8+ TILs was found in post-vaccine biopsies of patients who were not previously treated with immune-modulating cytokines or Ipilimumab. Interestingly, along with a maintained tumoral HLA class I expression, after DC vaccination we observed a significant increase of PDL1+ tumor cells, which significantly correlated with in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Flores I, Hevia D, Tittarelli A, Soto D, Rojas-Sepúlveda D, Pereda C, Tempio F, Fuentes C, Falcón-Beas C, Gatica J, Falcón-Beas F, Galindo M, Salazar-Onfray F, González FE, López MN Abstract Ovarian epithelial carcinoma (OEC) is the most frequent ovarian tumor, characterized by a high mortality in advanced stages where conventional therapies are not effective. Based on the role of the immune system in the progression of this disease, immunotherapy using checkpoint blockade has been considered as a therapeutic alternative. Nevertheless, its results do not match up to the p...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Treatments that generate T cell-mediated immunity to a patient ’s unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualiz...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
ConclusionsThese data suggest that a combined innate and adaptive immunotherapeutic approach can be effective against immunologically cold syngeneic murine neuroblastoma. Further testing is needed to determine how these concepts might translate into development of more effective immunotherapeutic approaches for the treatment of clinically high-risk neuroblastoma.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
We describe a model-based design strategy that was developed for a trial evaluating the safety and immunogenicity of vaccination with (1) peptides plus CD40 antibody and TLR3 ligand, (2) systemic administration of an agonistic CD27 antibody, and (3) to assess immune response from (1) and (2) compared to optimal controls in participants with stage IIB-IV melanoma.Results and conclusionsThe proposed design is a practical adaptive method for use with combined immunotherapy regimens with multiple objectives within multiple cohorts of interest. Further advances in the effectiveness of cancer immunotherapies will require new app...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
ConclusionOur results suggest that secondary resistance to immunotherapies can arise upon selection for new oncogenic variants that mediate T cell exclusion. To identify the spectrum of underlying mechanisms of therapeutic resistance, similar evaluation for the emergence of tumor-intrinsic alterations in resistant lesions should be done prospectively at the time of relapse in a range of additional patients developing secondary resistance.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Tumor neoantigens are ideal targets for cancer immunotherapy as they are recognized by host immune system as foreigners and can elicit tumor-specific immune responses. However, existing strategies utilizing RNA or long peptides for the neoantigen vaccines render limited immune responses since only 20–30% of neoantigens predicted in silico to bind MHC I molecules are capable of eliciting immune responses with the majority of responding T cells are CD4+. Therefore, it warrants further exploration to enhance neoantigen-specific CD8+ T cells responses. Since neoantigens are naturally weak antigens, we asked whether forei...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsIn summary,pTuneos provides the state-of-the-art one-stop and user-friendly solution for prioritizing SNV-based candidate neoepitopes, which could help to advance research on next-generation cancer immunotherapies and personalized cancer vaccines.pTuneos is available athttps://github.com/bm2-lab/pTuneos, with a Docker version for quick deployment athttps://cloud.docker.com/u/bm2lab/repository/docker/bm2lab/ptuneos.
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
ConclusionsThese data suggest that peripheral blood TCRB convergence may serve as a predictive or prognostic biomarker for response to dendritic cell-based immunotherapy. Our finding of increased T cell clonal expansion at week 5 of treatment supports the notion that TCR sequencing may serve as a tool for the measurement of pharmacodynamic markers of therapeutic agent activity. Ongoing and future studies will further clarify the utility of TCR convergence and clonal expansion as immune repertoire biomarkers.Clinical trial identificationNCT01876212.Legal entity responsible for the studyUniversity of Pittsburgh School of Med...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThis 5-year analysis represents the longest phase III follow-up for checkpoint inhibitor combination therapy and demonstrates long-term survival with both NIVO-containing arms vs IPI. In descriptive analyses, NIVO+IPI was associated with improved survival and a higher likelihood of being alive and treatment-free compared with NIVO alone, both without loss of QoL.Clinical trial identificationNCT01844505.Editorial acknowledgementWriting and editorial assistance was provided by Melissa Kirk, PhD, and Michele Salernitano of StemScientific, an Ashfield Company.Legal entity responsible for the studyBristol-Myers Squib...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
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