25,186 results match your criteria combination immunotherapy


Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort.

ESMO Open 2021 May 10;6(3):100118. Epub 2021 May 10.

Hematology and Oncology, Englander Institute for Precision Medicine Weill Cornell Medicine, New York-Presbyterian, New York, USA. Electronic address:

Background: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies.

Patients And Methods: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Read More

View Article and Full-Text PDF

Novel Therapies for Metastatic Triple-Negative Breast Cancer: Spotlight on Immunotherapy and Antibody-Drug Conjugates.

Oncology (Williston Park) 2021 May 13;35(5):249-254. Epub 2021 May 13.

Massachusetts General Hospital Cancer Center, Boston, MA.

Background: Triple-negative breast cancer (TNBC) is a biologically heterogeneous disease that is often associated with worse outcomes compared with other subtypes such as hormone receptor-positive tumors and HER2-positive tumors. While chemotherapy remains the mainstay of standard therapy for metastatic TNBC (mTNBC), several novel treatments have been developed over the past few years. In this review article, we review the major developments in the management of patients with mTNBC. Read More

View Article and Full-Text PDF

Safety and Efficacy of Neoadjuvant Immune Checkpoint Inhibitor Therapy in Patients with Resectable Non-small-Cell Lung Cancer: A Systematic Review.

Target Oncol 2021 May 13. Epub 2021 May 13.

Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli No 17, Beijing, 100021, People's Republic of China.

Background: Non-small-cell lung cancer (NSCLC) accounts for most new diagnoses of lung cancer, with high morbidity and mortality worldwide. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of metastatic and advanced NSCLC. For resectable NSCLC, while surgery is the cornerstone of standard treatment, a number of clinical trials of neoadjuvant immunotherapy have been conducted. Read More

View Article and Full-Text PDF

An Assessment of Combination of the Camrelizumab With Chemotherapy in Metastatic Biliary Tract Cancers.

Cancer Control 2021 Jan-Dec;28:10732748211017165

Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China.

Background: Monoclonal antibodies that target the PD-1 receptor are emerging as promising therapeutic candidates for the treatment of biliary tract cancers (BTCs). The purpose of the current study was to assess the combination of the camrelizumab with chemotherapy as a first-line treatment for metastatic BTCs.

Methods: We conducted a prospective single-arm pilot study of PD-1 antibody (camrelizumab 3 mg/kg d1, Q2 W or Q3 W) combined with different chemotherapy regimens as first-line treatment for BTCs. Read More

View Article and Full-Text PDF

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

Cancer Med 2021 May 12. Epub 2021 May 12.

Cancer Vaccine Development Program, San Antonio, TX, USA.

Background: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups. Read More

View Article and Full-Text PDF

Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model.

Cell Mol Immunol 2021 May 12. Epub 2021 May 12.

Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Gwangju, Korea.

The use of natural killer (NK) cells is a promising and safe immunotherapeutic approach in the field of cancer immunotherapy. However, combination treatments are required to enhance the effector functions and therapeutic efficacy of NK cells. In this study, we investigated the potential of daratumumab (Dara), bortezomib, and dexamethasone (Dvd) to augment the antitumor effects of NK cells in a multiple myeloma (MM) xenograft mouse model. Read More

View Article and Full-Text PDF

DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells.

J Immunother Cancer 2021 May;9(5)

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain

Background: Conventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet. Read More

View Article and Full-Text PDF

Anti-PD-1 checkpoint blockade improves the efficacy of a melphalan-based therapy in experimental melanoma.

Eur J Surg Oncol 2021 May 4. Epub 2021 May 4.

TIMM Laboratory, Sahlgrenska Center for Cancer Research, Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Introduction: The induction of adaptive cellular immunity in patients with in-transit melanoma metastasis treated with hyperthermic isolated limb perfusion (ILP) with melphalan has been shown to contribute to the effectiveness of the therapy. Activated CD8 T cells appear to be of particular importance for the efficacy of melphalan-based ILP therapy, as observed in both patients and animal models. In this study, we explored the possible synergistic effects of combining melphalan-based therapy with the checkpoint inhibitor anti-PD-1 on tumours in a mouse melanoma model. Read More

View Article and Full-Text PDF

Immunotherapy for Advanced Non-Small Cell Lung Cancer: A Decade of Progress.

Am Soc Clin Oncol Educ Book 2021 Mar;41:1-23

Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida,Tampa, FL.

The treatment paradigm for patients with advanced non-small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non-small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti-vascular endothelial growth factor drugs. Read More

View Article and Full-Text PDF

Anti-angiogenic and macrophage-based therapeutic strategies for glioma immunotherapy.

Brain Tumor Pathol 2021 May 11. Epub 2021 May 11.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

As a new concept of glioma therapy, immunotherapy combined with standard therapies is a promising modality to improve glioma patient survival. VEGF and its signaling pathway molecules not only inhibit angiogenesis but also may reinforce the immunosuppressive tumor microenvironment, including promotion of the accumulation of immunosuppressive tumor-associated macrophages (TAMs). In this review, we discuss VEGF-targeted therapy as a new treatment option of the TAM-targeted therapy for high-grade gliomas, as well as other TAM-targeted therapies. Read More

View Article and Full-Text PDF

Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome.

Cancer Immunol Immunother 2021 May 11. Epub 2021 May 11.

Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. Read More

View Article and Full-Text PDF

Recurrent spindle cell carcinoma of the lung successfully treated by chemoimmunotherapy.

Respirol Case Rep 2021 Jun 7;9(6):e00757. Epub 2021 May 7.

Department of Respiratory Medicine Tokyo Women's Medical University Tokyo Japan.

There is limited evidence for the treatment of sarcomatoid lung carcinoma, especially spindle cell carcinoma (SpCC) because of the rarity of disease. Although the efficacy of combination of chemotherapy and immunotherapy (i.e. Read More

View Article and Full-Text PDF

Oridonin inhibits tumor angiogenesis and induces vessel normalization in experimental colon cancer.

J Cancer 2021 2;12(11):3257-3264. Epub 2021 Apr 2.

Department of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi 030012, China.

Tumor blood vessels exhibit morphological and functional aberrancies. Its maturity and functionality are closely associated with colon cancer progression and therapeutic efficacy. The direct evidence proving whether oridonin (ORI) has vascular normalization promoting effect from which combination therapies will benefit is still lacking. Read More

View Article and Full-Text PDF

FUT8-mediated aberrant N-glycosylation of B7H3 suppresses the immune response in triple-negative breast cancer.

Nat Commun 2021 May 11;12(1):2672. Epub 2021 May 11.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Most patients with triple negative breast cancer (TNBC) do not respond to anti-PD1/PDL1 immunotherapy, indicating the necessity to explore immune checkpoint targets. B7H3 is a highly glycosylated protein. However, the mechanisms of B7H3 glycosylation regulation and whether the sugar moiety contributes to immunosuppression are unclear. Read More

View Article and Full-Text PDF

The MNK1/2-eIF4E axis supports immune suppression and metastasis in postpartum breast cancer.

Cancer Res 2021 May 11. Epub 2021 May 11.

Goodman Cancer Research Center, McGill University.

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes translation of pro-metastatic mRNAs in tumor cells, but its role in modulating the function of non-tumor cells in the PPBC microenvironment has not been explored. Read More

View Article and Full-Text PDF

KEYNOTE-859: a Phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma.

Future Oncol 2021 May 12. Epub 2021 May 12.

PLA Cancer Centre of Nanjing, Jinling Hospital, Nanjing, 34210002, China.

Current guidelines recommend two-drug cytotoxic chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) and a platinum-based agent (oxaliplatin or cisplatin) as first-line treatment for advanced gastric cancer. Pembrolizumab monotherapy has demonstrated durable antitumor activity in patients with advanced programmed death ligand 1-positive (combined positive score ≥1) gastric/gastroesophageal junction adenocarcinoma. Accumulating evidence indicates that combining pembrolizumab with standard-of-care chemotherapy for the treatment of advanced or metastatic cancer improves clinical outcomes. Read More

View Article and Full-Text PDF

Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy.

MAbs 2021 Jan-Dec;13(1):1913791

Roche Innovation Center Zurich, Zurich, Switzerland.

Simlukafusp alfa (FAP-IL2v, RO6874281/RG7461) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAP) and an IL-2 variant with a retained affinity for IL-2Rβγ > IL-2 Rβγ and abolished binding to IL-2 Rα. Here, we investigated the immunostimulatory properties of FAP-IL2v and its combination with programmed cell death protein 1 (PD-1) checkpoint inhibition, CD40 agonism, T cell bispecific and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. The binding and immunostimulatory properties of FAP-IL2v were investigated and compared with FAP-IL2wt. Read More

View Article and Full-Text PDF

Doxorubicin and PD-L1 siRNA co-delivery with stem cell membrane-coated polydopamine nanoparticles for the targeted chemoimmunotherapy of PCa bone metastases.

Nanoscale 2021 May 11. Epub 2021 May 11.

Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun, China.

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. Read More

View Article and Full-Text PDF

Cell-free DNA copy number variations predict efficacy of immune checkpoint inhibitor-based therapy in hepatobiliary cancers.

J Immunother Cancer 2021 May;9(5)

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Background: This study was designed to screen potential biomarkers in plasma cell-free DNA (cfDNA) for predicting the clinical outcome of immune checkpoint inhibitor (ICI)-based therapy in advanced hepatobiliary cancers.

Methods: Three cohorts including 187 patients with hepatobiliary cancers were recruited from clinical trials at the Peking Union Medical College Hospital. Forty-three patients received combination therapy of programmed cell death protein 1 (PD-1) inhibitor with lenvatinib (ICI cohort 1), 108 patients received ICI-based therapy (ICI cohort 2) and 36 patients received non-ICI therapy (non-ICI cohort). Read More

View Article and Full-Text PDF

Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Clin Lung Cancer 2021 Mar 27. Epub 2021 Mar 27.

Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Cancer Institute, Duke University, Durham, NC. Electronic address:

Introduction: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC.

Methods: We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Read More

View Article and Full-Text PDF

CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials.

Lung Cancer 2021 May 5. Epub 2021 May 5.

Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address:

The aim of adoptive T-cell therapy is to promote tumor-infiltrating immune cells following the transfer of either tumor-harvested or genetically engineered T lymphocytes. A new chapter in adoptive T-cell therapy began with the success of chimeric antigen receptor (CAR) T-cell therapy. T cells harvested from peripheral blood are transduced with genetically engineered CARs that render the ability to recognize cancer cell-surface antigen and lyse cancer cells. Read More

View Article and Full-Text PDF

Identification of an immune classification for cervical cancer and integrative analysis of multiomics data.

J Transl Med 2021 May 10;19(1):200. Epub 2021 May 10.

Department of Radiation Oncology, First Hospital of China Medical University, Heping District, Shenyang,, Liaoning, China.

Background: To understand the molecular mechanisms of the antitumour response, we analysed the immune landscape of cervical cancer to identify novel immune molecular classes.

Methods: We established a stable immune molecular classification using a nonnegative matrix factorization algorithm and validated the correlation in two validation sets of 249 samples.

Results: Approximately 78% of cervical cancers (CCs) (228/293) were identified to show significant enrichment in immune cells (e. Read More

View Article and Full-Text PDF

Immunotherapy for pancreatic cancer.

World J Clin Cases 2021 May;9(13):2969-2982

Department of Internal Medicine, University of Hallym College of Medicine, Hallym University Sacred Heart Hospital, Anyang 14068, South Korea.

Pancreatic cancer, a highly lethal cancer, has the lowest 5-year survival rate for several reasons, including its tendency for the late diagnosis, a lack of serologic markers for screening, aggressive local invasion, its early metastatic dissemination, and its resistance to chemotherapy/radiotherapy. Pancreatic cancer evades immunologic elimination by a variety of mechanisms, including induction of an immunosuppressive microenvironment. Cancer-associated fibroblasts interact with inhibitory immune cells, such as tumor-associated macrophages and regulatory T cells, to form an inflammatory shell-like desmoplastic stroma around tumor cells. Read More

View Article and Full-Text PDF

Radiotherapy in the Era of Immunotherapy With a Focus on Non-Small-Cell Lung Cancer: Time to Revisit Ancient Dogmas?

Front Oncol 2021 21;11:662236. Epub 2021 Apr 21.

Department of Radiotherapy, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France.

Radiation-induced immune effects have been extensively deciphered over the last few years, leading to the concept of the dual immune effect of radiotherapy with both immunostimulatory and immunosuppressive effects. This explains why radiotherapy alone is not able to drive a strong anti-tumor immune response in most cases, hence underlining the rationale for combining both radiotherapy and immunotherapy. This association has generated considerable interest and hundreds of trials are currently ongoing to assess such an association in oncology. Read More

View Article and Full-Text PDF

Analysis of Adenoviral p53 Gene Therapy Clinical Trials in Recurrent Head and Neck Squamous Cell Carcinoma.

Front Oncol 2021 22;11:645745. Epub 2021 Apr 22.

University of Toledo Medical Center, Eleanor N. Dana Cancer Center, Toledo, OH, United States.

Background: We conducted an analysis of previous adenoviral p53 (Ad-p53) treatment data in recurrent head and neck squamous cell carcinoma (HNSCC) patients to identify optimal Ad-p53 treatment methods for future clinical trials.

Methods: The analysis involved recurrent HNSCC patients treated with Ad-p53 for whom p53 genotyping and immunohistochemistry tumor biomarker studies had been performed (n = 70). Ad-p53 tumor treatment responses defined by RECIST 1. Read More

View Article and Full-Text PDF

Application of Antibody Fragments Against Aβ With Emphasis on Combined Application With Nanoparticles in Alzheimer's Disease.

Front Pharmacol 2021 22;12:654611. Epub 2021 Apr 22.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and accumulating evidences suggest a key role of amyloid-β (Aβ) peptide in the pathogenesis of AD. According to the amyloid cascade hypothesis, the imbalance of producing and clearing Aβ is the beginning of neurodegeneration and dementia. Consequently, immunotherapy becomes popular through using antibodies against Aβ. Read More

View Article and Full-Text PDF

Targeted therapies for gallbladder cancer: an overview of agents in preclinical and clinical development.

Expert Opin Investig Drugs 2021 May 8. Epub 2021 May 8.

Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases,IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Introduction: Gallbladder Cancer (gc) Is A Rare Malignancy With A Dismal Prognosis. If It Is Diagnosed Early Enough, It Can Be Cured By Surgical Removal. Unfortunately, Only A Small Gc Patient Population Can Be Amenable To Surgery, Though, With A High Relapse Rate. Read More

View Article and Full-Text PDF

Brief in vitro IL-12 conditioning of CD8 T Cells for anticancer adoptive T cell therapy.

Cancer Immunol Immunother 2021 May 8. Epub 2021 May 8.

Animal Section, Department of Biological Sciences, Faculty of Science, Taibah University, Medina, Saudi Arabia.

Cancer immunotherapy represents a potential treatment approach through non-specific and specific enhancement of the immune responses. Adoptive cell therapy (ACT) is a potential modality of immunotherapy that depends on harvesting T cells from the tumor-bearing host, activating them in vitro and infusing them back to the same host. Several cytokines, in particular IL-2, IL-7 and IL-15, have been used to enhance survival T cells in vitro. Read More

View Article and Full-Text PDF

Amlexanox enhances the antitumor effect of anti-PD-1 antibody.

Biochem Biophys Res Commun 2021 May 6;560:1-6. Epub 2021 May 6.

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.

Cancer immunotherapy, especially treatment with monoclonal antibodies (mAbs) that block programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling, has attracted attention as a new therapeutic option for cancer. However, only a limited number of patients have responded to this treatment approach. In this study, we searched for compounds that enhance the efficacy of anti-PD-1 mAb using mixed lymphocyte reaction (MLR), which is a mixed culture system of the two key cells (dendritic and T cells) involved in tumor immunity. Read More

View Article and Full-Text PDF

Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma.

J Immunother Cancer 2021 May;9(5)

Providence Cancer Institute, Portland, Oregon, USA

Background: Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone.

Methods: The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Read More

View Article and Full-Text PDF