Search results for "Immunotherapy."

Mast cells boost myeloid-derived suppressor cell activity and contribute to the development of tumor-favoring microenvironment

2014

Abstract Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells is emerging as critical for the outcome of the tumor-associated immune response. Herein, we showed the occurrence of cell-to-cell interactions between MDSCs and mast cells in the mucosa of patients with colon carcinoma and in the colon and spleen of tumor-bearing mice. Furthermore, we demonstrated that the CT-26 colon cancer cells induced the accumulation of CD11b+Gr1+ imma…

Dendritic cell-tumor cell hybrids and immunotherapy: what's next?

2011

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, …

mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA

2013

Abstract Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 mela…

Heat Shock Protein Vaccines Against Cancer

1993

Vaccination of mice with heat shock proteins (HSPs) derived from a tumor makes the mice resistant to the tumor from which the HSP was obtained. This phenomenon has been demonstrated with three HSPs--gp96, hsp90, and hsp70. Vaccination with HSPs also elicits antigen-specific cytotoxic T lymphocytes (CTLs). The specific immunogenicity of HSPs derives apparently, not from the HSPs per se, but from the peptides bound to them. These observations provide the basis for a new generation of vaccines against cancer. The HSP-based cancer vaccines circumvent two of the most intractable hurdles to cancer immunotherapy. One of them is the possibility that human cancers, like cancers of experimental anima…

Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines.

2013

Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In prevent…

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab

2023

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.Patients and methodsThis is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with aveluma…

Addressing tumour tolerance to improve cancer immunotherapy

2010

Systemic therapies for hepatocellular carcinoma: The present and the future

2021

Hepatocellular carcinoma is diagnosed in more than half of all cases at unresectable stage when no potentially curative treatments are feasible. Since 2008, sorafenib had represented the only effective first line systemic therapy over the last decade until the approval of lenvatinib, who showed to be non-inferior to sorafenib. Recently, for the first time, a combination of immunotherapy and antiangiogenic drug, atezolizumab plus bevacizumab, was associated with a significantly longer overall survival and progression free survival compared to sorafenib, becoming the new best performing first-line approach for unresectable HCC. After several randomized controlled trials (RCTs) that have attem…

Immune Control in Hepatocellular Carcinoma Development and Progression: Role of Stromal Cells

2014

Immune control of hepatocellular carcinoma (HCC) is executed by effector immune cells, which efficiently eliminate malignant transformed cells. However, progression of HCC clearly documents failure of tumor immune control, which led to the concept of immune subversion by the tumor environment. Particularly tumor-associated stromal cells cooperate within an inflammatory network, which is responsible for immune privilege. The stromal cell composition matures during tumor growth and is derived from surrounding noncancerous tissue or from circulating cells recruited to the tumor site. Therefore, immunosuppressive stromal cells represent heterogeneous cell lineages, including myeloid cells, lymp…

From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: A translational overview

2019

Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated…