The Prognostic Role of High Blood Cholesterol in Advanced Cancer Patients Treated With Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICI) have improved survival in numerous types of cancer. However, a great number of unselected patients still do not respond to ICI. Moreover, there is a need to identify biomarkers that could predict the prognosis of immunotherapy-treated patients. The aim of our study is to evaluate the prognostic value of baseline plasmatic cholesterol levels in metastatic cancer patients treated with immunotherapy. We retrospectively enrolled advanced cancer patients consecutively treated with ICI at our center between October 2013 and October 2018 to correlate the blood cholesterol level before treatment ...
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Advanced Non–Small Cell Lung Cancer Patients With Low Tumor Mutation Burden Might Derive Benefit From Immunotherapy
The aim of this study is to investigate the association between tumor mutation burden (TMB) and survival in non–small cell lung cancer (NSCLC) patients with anti-programmed cell death protein 1 and anti-programmed death-ligand 1 blockade. Two retrospective cohorts and The Cancer Genome Atlas NSCLC data set were included in this study. The restricted cubic spline analysis was used to explore the association between TMB and survival. The cutoff values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS). The associations between TMB and intratumor heterogeneity, number of segments, fracti...
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma
B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein expressed on malignant plasma cells of patients with multiple myeloma (MM), and it is a defined therapeutic target. Major histocompatibility complex class I-related chain A (MICA) is frequently expressed in lymphoproliferative malignancies including MM. MICA activates natural killer (NK) cells and costimulates T cells by interaction with its immunoreceptor NK cell receptor G2D (NKG2D). Nonetheless, during full-blown MM, tumor cells promote efficient MICA shedding, which evokes NKG2D internalization and immune suppression. To enhance the directional ...
Source: Journal of Immunotherapy - June 11, 2020 Category: Allergy & Immunology Tags: Basic Study Source Type: research
Expression of Programmed Cell Death Proteins in Kaposi Sarcoma and Cutaneous Angiosarcoma
Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS,...
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Paraneoplastic Encephalitis and Enteric Neuropathy Associated With Anti-Hu Antibody in a Patient Following Immune-checkpoint Inhibitor Therapy
This article reports a case of paraneoplastic encephalitis and enteric neuropathy associated with anti-Hu antibody in a patient with advanced small cell lung cancer. Symptoms presented in the third week after the second dose of sintilimab therapy and manifested as focal seizures and intestinal pseudo-obstruction. The patient’s neurological symptoms improved significantly after treatment with intravenous infusion of methylprednisolone and sequential oral prednisone. This is the first report of sintilimab-related neurological adverse events. On the basis of this case, we speculate that ICIs may induce PNSs. Identifying rel...
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Study on the Expression Levels and Clinical Significance of PD-1 and PD-L1 in Plasma of NSCLC Patients
This study provides a reference for the assessment of prognosis and risk stratification for NSCLC patients, as well as for immune treatment of cancer. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
A Case of Response to Immunotherapy in a Patient With MSI Metastatic Colorectal Cancer and Autoimmune Disease Receiving Steroid Therapy
We present the case of a 74-year-old man with pulmonary autoimmune intersitiopathy and microsatellite instability metastatic colorectal cancer who responded to nivolumab despite the concomitant steroid therapy. Furthermore, his autoimmune disease did not worsen during immunotherapy. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - May 13, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Successful Treatment of In-Transit Metastatic Melanoma in a Renal Transplant Patient With Combination T-VEC/Imiquimod Immunotherapy
We present a case of in-transit metastatic melanoma in a renal transplant patient. The patient was initially managed with talimogene laherparepvec (T-VEC) injections alone with continued local progression. Addition of topical imiquimod 5% cream to intralesional T-VEC resulted in a rapid and dramatic response, with complete clearance of the cutaneous in-transit metastases and without any sign of organ rejection. In solid organ transplant patients who lack surgical options and are not eligible for treatment with a BRAF inhibitor, and for whom treatment with checkpoint inhibitors present risk of organ rejection, T-VEC either ...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Complete Recovery of Immune Checkpoint Inhibitor–induced Colitis by Diverting Loop Ileostomy
We present a case of recurrent episodes of checkpoint inhibitor–induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Positive Status of Epstein-Barr Virus as a Biomarker for Gastric Cancer Immunotherapy: A Prospective Observational Study
Immunotherapy has exhibited promising but controversial results in gastric cancer; determining criteria for choosing the appropriate target population is still problematic. Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) exhibits distinctive genomic aberrations and clinicopathologic features, the positive status of EBV is a potential biomarker. We prospectively recruited 9 patients who were diagnosed with stage-IV EBVaGC, and all of the patients were treated by immune-checkpoint inhibitors. The median age of the patients was 62 years old. The clinicopathologic characteristics demonstrated a male predominance...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Pembrolizumab Treatment and Pathologic Therapeutic Evaluation for Granulocyte Colony-stimulating Factor-producing Bladder Cancer: A Case Report and Literature Review
We report a case of the pathologically evaluated antitumor effect of pembrolizumab, a programmed death-1 immune checkpoint inhibitor antibody, in G-CSF-producing bladder cancer. A 53-year-old male patient underwent 4 courses chemotherapy with a combination of gemcitabine and carboplatin before a radical cystectomy with ileal neobladder. Four months after the surgery, local recurrence was detected in the pelvis and therefore pembrolizumab was used. One week after its administration, the patient showed increased mucus in his urine. A computed tomography scan and cystoscopy revealed a fistula between the ileum and the neoblad...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Patched 1-interacting Peptide Represses Fibrosis in Pancreatic Cancer to Augment the Effectiveness of Immunotherapy
We examined the influence of a Hedgehog signal inhibitor, Patched 1-interacting peptide, on fibrosis, infiltration of immune cells, and immunotherapeutic effects on PDAC. We found that this peptide inhibited proliferation and migration of cancer-associated fibroblasts and cancer cells. Furthermore, this peptide reduced the production of extracellular matrix and transforming growth factor β1 in cancer-associated fibroblasts and induced expression of HLA-ABC in PDAC cells and interferon-γ in lymphocytes. In vivo, the peptide suppressed fibrosis of PDAC and increased immune cell infiltration into tumors. The combination of ...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Antitumor Potency of an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, Lisocabtagene Maraleucel in Combination With Ibrutinib or Acalabrutinib
This study assessed the in vitro and in vivo functionality of CAR T cells transduced to express the anti-CD19 CAR of liso-cel in combination with ibrutinib or acalabrutinib. In prolonged stimulation assays, the presence of ibrutinib or acalabrutinib improved the CAR T-cell effector function. RNA-Seq analysis and surface marker profiling of these CAR T cells treated with ibrutinib but not acalabrutinib revealed gene expression changes consistent with skewing toward a memory-like, type 1 T-helper, Bruton tyrosine kinase phenotype. Ibrutinib or acalabrutinib improved CD19+ tumor clearance and prolonged survival of tumor-beari...
Source: Journal of Immunotherapy - April 10, 2020 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Brief Communication: Immune Checkpoint Inhibitor-induced Diaphragmatic Dysfunction: A Case Series
Diaphragmatic dysfunction is a rare cause of dyspnea that can lead to hypercapnic respiratory failure. A variety of causes of diaphragmatic dysfunction have been identified, including myopathies and neuropathies, the latter of which can be further subdivided into infectious, idiopathic, demyelinating, malignant, and iatrogenic etiologies. Now, in the era of immune checkpoint inhibitors (ICIs), case reports of immune-mediated phrenic nerve palsies have been described. This diagnosis can be challenging to make, as dyspnea is a common presenting complaint and immune-mediated palsy of the phrenic nerve is a rarely described co...
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
The Anticancer Efficacy of Immune Checkpoint Inhibitors According to Patients’ Age: A Systematic Review and Meta-Analysis
Limited prospective data about the activity of immune checkpoint inhibitors (ICIs) are available for elderly patients. The aim of our analysis was to determine the relative efficacy of ICIs versus available standard therapies [standard of care (SOC)] in subgroups defined by patients’ age. Searching the MEDLINE/PubMed, Cochrane Library, and American Society of Clinical Oncology (ASCO) Meeting abstracts randomized clinical trials were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The measured outcome was overall survival (OS)....
Source: Journal of Immunotherapy - March 10, 2020 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
