A Brief Communication on Circulating PD-1-positive T-Regulatory Lymphocytes in Melanoma Patients Undergoing Adjuvant Immunotherapy With Nivolumab
Upregulation of T-regulatory lymphocytes (Tregs) is one of numerous immune escape mechanisms of malignancies. In the present pilot study we aimed to study the effect of adjuvant nivolumab during the initiation of treatment on circulating Tregs subpopulations in patients with stage III melanoma. We subsequently recruited patients with stage III melanoma who had the indication for adjuvant anti-programmed death 1 (PD-1) treatment with nivolumab. Blood collections were performed before the initiation of nivolumab and before every 2-week therapy cycle. Flow cytometry was performed for the determination of circulating CD4+CD25h...
Source: Journal of Immunotherapy - August 9, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
Prognostic Significance of Hematological Indices in Malignant Melanoma Treated With Immune Checkpoint Inhibitors
Local and systemic inflammation significantly effects tumor progression and its response to therapy. We aim to evaluate the prognostic significance of inflammatory cells, their ratios, and a change in these indices while patients are receiving immune checkpoint inhibitors (ICIs). We retrospectively reviewed 120 malignant melanoma patients who had received any ICIs from 2011 until December 2017 and evaluated the effect of hematological indices on survival and radiographic responses. We followed the trends of these indices at 0, 6, and 12 weeks while on ICIs. Univariate and multivariate survival analyses were performed. The ...
Source: Journal of Immunotherapy - August 9, 2019 Category: Allergy & Immunology Tags: Clincal Studies Source Type: research
Identification of a Promiscuous Epitope Peptide Derived From HSP70
We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I–binding peptides, we selected candidates that bound to>2 of the 3 HLA types. ...
Source: Journal of Immunotherapy - August 9, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
The VE-PTP Inhibitor AKB-9778 Improves Antitumor Activity and Diminishes the Toxicity of Interleukin 2 (IL-2) Administration
Administration of interleukin (IL)-2 has led to a durable response in patients with advanced renal cancer and melanoma but is restricted for clinical application because of adverse effects, including the vascular leak syndrome (VLS). VLS is associated with increased circulating levels of the Tie2 antagonist ligand, angiopoietin 2, and decreased Tie2 receptor phosphorylation and downstream signaling in endothelial cells (ECs). Given that vascular endothelial protein tyrosine phosphatase (VE-PTP) is a specific membrane phosphatase in ECs that dephosphorylates Tie2, the effects of targeting VE-PTP by a selective inhibitor AKB...
Source: Journal of Immunotherapy - August 9, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Racial and Socioeconomic Disparities in the Delivery of Immunotherapy for Metastatic Melanoma in the United States
This study addressed a crucial public health priority by evaluating disparities in administration of immunotherapy for metastatic melanoma. The National Cancer Database was queried for newly diagnosed metastatic melanoma. Patients were dichotomized based on receipt of immunotherapy based on National Cancer Database coding. Multivariable logistic regression ascertained factors associated with immunotherapy delivery. Subgroup analysis evaluated the interaction between race, insurance status, and income. Secondarily, Cox multivariate and propensity-matched Kaplan-Meier analyses assessed overall survival based on immunotherapy...
Source: Journal of Immunotherapy - June 12, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Clinical Correlates of Response to Anti-PD-1–based Therapy in Patients With Metastatic Melanoma
Anti-PD-1 agents, alone or in combination with ipilimumab, produce durable responses in some melanoma patients. Tumor features that correlate with response are not well defined. We collected clinical data from metastatic melanoma patients treated at 2 centers who received anti-PD-1 (n=303) or anti-PD-1+ipilimumab (n=57). We correlated number of metastases, diameter of largest tumor (tumor bulk), and organ involvement with response rate (RR), progression-free survival (PFS), and overall survival (OS). Patients with diameter of largest tumor ≤2 cm had a 53% RR, whereas those with largest tumor>2 cm had a 38% RR (P=0.00...
Source: Journal of Immunotherapy - June 12, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Variation of Programmed Death Ligand 1 Expression After Platinum-based Neoadjuvant Chemotherapy in Lung Cancer
The effect of chemotherapy on programmed cell death-ligand 1 (PD-L1) expression has been previously studied in lung cancer, while the results remain controversial. The aim of this study was to investigate the variation of PD-L1 expression after neoadjuvant chemotherapy and explore the association between chemotherapy response, prognosis and the variation of PD-L1 expression in lung cancer patients. A total of 63 lung cancer patients who received platinum-based neoadjuvant chemotherapy and subsequently underwent surgical resection were selected. PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) w...
Source: Journal of Immunotherapy - June 12, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Association Between Pembrolizumab-related Adverse Events and Treatment Outcome in Advanced Melanoma: Results From the Dutch Expanded Access Program
In this study, we aim to evaluate this association for pembrolizumab. To this end, data of 147 patients included in the Dutch cohort of the Pembrolizumab Expanded Access Program were collected. All data were collected prospectively. Patients with adverse events (AEs) at any time during therapy showed a higher chance of achieving disease control compared with patients without AEs (low-grade AEs vs. no AEs: odds ratio=12.8, P=0.0002, high-grade AEs vs. no AEs: odds ratio=38.5, P=0.0001) according to a multivariate logistic regression analysis. In addition, Cox regression analysis showed a lower risk of death (hazard ratio: 0...
Source: Journal of Immunotherapy - June 12, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Preferential Homing of Tumor-specific and Functional CD8+ Stem Cell-like Memory T Cells to the Bone Marrow
The bone marrow (BM) harbors not only hematopoietic stem cells but also conventional memory T and B cells. Studies of BM-resident memory T cells have revealed the complex relationship between BM and immunologic memory. In the present study, we identified CD122high stem cells antigen-1 (Sca-1)high, B-cell lymphoma protein-2 (Bcl-2)high, CD8+ stem cell-like memory T cells (TSCMs) as a distinct memory T-cell subset preferentially residing in the BM, where these cells respond vigorously to blood-borne antigens. We found that the most TSCMs favorably relocate to the BM by adhesion molecules such as vascular cell adhesion protei...
Source: Journal of Immunotherapy - June 12, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
“Acquired” NKG2D Ligand Stimulates NK Cell–mediated Tumor Immunosurveillance
Engagement of activating receptor NKG2D to its ligand mediates natural killer (NK) cell activation and enhances cytotoxicity. NKG2D ligands (NKG2DLs) are frequently expressed on the tumor cell surface. However, the expression patterns of different NKG2DLs vary between tumor cells. Downregulation of certain ligand enables the tumor cells to escape NK cell–mediated immunosurveillance. By generating tumor cell lines with high expression of NKG2D ligand MULT1, we aimed to explore the function of NKG2DLs diversity on the activation and regulation of NKG2D signaling pathway. NK cells were potently activated by the “acquired...
Source: Journal of Immunotherapy - June 12, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Functionally Defective T Cells After Chemotherapy of B-Cell Malignancies Can Be Activated by the Tetravalent Bispecific CD19/CD3 Antibody AFM11
In conclusion, T cells from lymphoma patients are reduced in number and have functional defects following treatment with certain chemotherapy regimens, also reducing AFM11 efficacy. Importantly, AFM11 was still able to trigger B-cell-directed T-cell immunity in all treatment groups. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 16, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Incidence and Clinical Impact of Anti-TNFα Treatment of Severe Immune Checkpoint Inhibitor-induced Colitis in Advanced Melanoma: The Mecolit Survey
Immune checkpoint inhibitors (ICI) significantly improve overall survival (OS) in patients with advanced melanoma, but immune-related colitis may occur and warrant anti-tumor necrosis factor α (TNFα) treatment in severe forms. A nationwide, multicenter retrospective survey was conducted to assess both, the real-life incidence of grade 3/4 ICI-induced colitis treated with anti-TNFα, in patients with advanced melanoma, and the consequence of this therapeutic strategy on disease outcome. All patients with advanced melanoma treated with anti-TNFα agents for severe ICI-related colitis in the participating centers were inclu...
Source: Journal of Immunotherapy - May 16, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
UV Light–inactivated HSV-1 Stimulates Natural Killer Cell–induced Killing of Prostate Cancer Cells
Herein we demonstrate that ultraviolet light–inactivated Herpes Simplex Virus-1 (UV-HSV-1) stimulates peripheral blood mononuclear cells (PBMCs) to lyse both androgen-sensitive and androgen-independent prostate cancer (PrCA) cell lines, but not the benign prostatic hyperplastic epithelial cell line, BPH-1, and is 1000–10,000-fold more potent at stimulating this killing than ultraviolet light-inactivated Vesicular Stomatitis Virus, adenovirus, reovirus or cytomegalovirus. Among PBMCs, natural killer (NK) cells appear to be a major cell type involved in this killing and UV-HSV-1 appears to directly and potently stimulate...
Source: Journal of Immunotherapy - May 16, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Role of Interferon (IFN)α in “Cocktails” for the Generation of (Leukemia-derived) Dendritic Cells (DCleu) From Blasts in Blood From Patients (pts) With Acute Myeloid Leukemia (AML) and the Induction of Antileukemic Reactions
Strategies to stabilize remissions by specific elimination of residual acute myeloid leukemia (AML) blasts are needed. Leukemia-derived dendritic cell (DCleu/DC) generated from myeloid blasts improve antileukemic T-cell reactivity and install T-cell memory. Interferon (IFN)α-DC methods produce DCleu from chronic myeloid leukemia-patients (pts’) blood. Various INFα-containing versus other DC methods were studied to produce DCleu (evaluated by flowcytometry) from AML-pts’ blast-containing mononuclear (MNC) or whole blood (WB). After DCleu/DC stimulation in mixed lymphocyte cultures, T cells’ potential to gain antileu...
Source: Journal of Immunotherapy - May 16, 2019 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Response to the Rechallenge With Talimogene Laherparepvec (T-VEC) After Ipilimumab/Nivolumab Treatment in Patient With Cutaneous Malignant Melanoma Who Initially Had a Progression on T-VEC With Pembrolizumab
Talimogene laherparepvec (T-VEC) is approved for unresected stage III–IV malignant melanoma. T-VEC has a direct cytotoxic effect and enhances the antitumor immunity of host cells. Immune checkpoints inhibitors also enhance the immunity of host cells by increasing the recruitment of antigen-presenting cells or activation and restoration of T-cell functions. Both type of therapies can potentiate the effect of the other therapy. We are reporting a case of T-VEC rechallenge who initially progressed on T-VEC with pembrolizumab but then responded to T-VEC rechallenge after intervening ipilimumab/nivolumab. An 83-year-old man d...
Source: Journal of Immunotherapy - April 11, 2019 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
