Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery

Abstract Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4 %. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cel...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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AbstractNon-small cell lung cancer (NSCLC) has been threatening human health for years. Cytotoxicity-based chemotherapy seems to reach plateau in NSCLC treatment. Immunotherapy with immune checkpoint inhibitors (ICIs) against programmed cell death 1 (PD-1/L1) axis are to provide long-term survival benefits for wild-type advanced NSCLC patients with acceptable adverse effects. Though beneficiary population is limited from monotherapy, combination strategies are expanding indicators. Retrospective evidences suggested ICIs are also potentially useful for brain metastasis. Furthermore, the combination of ICIs and surgery are t...
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
AbstractImmunotherapy has led to a paradigm shift in the treatment of many advanced malignancies. Despite the success in treatment of tumors like non-small cell lung cancer (NSCLC) and melanoma, checkpoint inhibition-based immunotherapy has limitations. Many tumors, such as pancreatic cancer, are less responsive to checkpoint inhibitors, where patients tend to have a limited duration of benefit and where clinical responses are more robust in patients who are positive for predictive biomarkers. One of the critical factors that influence the efficacy of immunotherapy is the tumor microenvironment (TME), which contains a hete...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
An AstraZeneca immunotherapy has failed to meet its goal in a late-stage study involving patients with advanced non-small cell lung cancer.
Source: - Category: Pharmaceuticals Source Type: news
Condition:   Lung Cancer Interventions:   Other: Bronchoscopy;   Other: Research Procedures Sponsors:   NYU Langone Health;   National Cancer Institute (NCI) Not yet recruiting
Source: - Category: Research Source Type: clinical trials
Combination including immunotherapy drug Imfinzi did not deliver hoped-for results
Source: - Drugs and Healthcare - Category: Pharmaceuticals Source Type: news
Here, we report a case of myasthenia gravis and myopathy in a patient treated with nivolumab. A 76 ‐year‐old man who had been treated with four doses of nivolumab because of non‐small cell lung cancer (NSCLC) presented with proximal‐dominant muscle weakness and fluctuating ptosis and diplopia. Serologic studies revealed increased levels of muscle enzymes including creatine phosphokinase ( 2934 U/L), and acetylcholine receptor antibody was positive (1.31 nmol/L). Following electrodiagnostic study, he was diagnosed with myasthenia gravis and active stage of myopathy. After discontinuation of nivolumab, he was treated...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research
The authors regret the Cancer Prevention Research Institute of Texas Grant RP110584 was incorrectly noted; it should be RP150535.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Tags: Corrigendum Source Type: research
Authors: Tsoukalas N, Theocharis MKKTMTEAFPBGKS Abstract The integration of immunotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC) has revolutionized the approach of the prevalent type of lung cancer. Although PD-1 and its ligands (PD-L1 and PD-L2) are stimulating molecules of the immune-checkpoint pathway, with primary function to limit inflammatory response and autoimmunity, tumor cells have found a way to exploit these molecules by obtaining the opportunity to respond with PD-L1 expression in cytokine signals and thus to evade immune surveillance. Several immunotherapeutic agents targeti...
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
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Source: Seminars in Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: THORACIC – Editorial Commentary Source Type: research
AbstractMHC class I-related chain A (MICA) is one of the major ligands for natural killer group 2 member D (NKG2D), which is an activating NK receptor. MICA is expressed on the surface of human epithelial tumor cells, and its shedding from tumor cells leads to immunosuppression. To activate immune response in the tumor microenvironment, we designed an anti-VEGFR2 –MICA bispecific antibody (JZC01), consisting of MICA and an anti-VEGFR2 single chain antibody fragment (JZC00) and explored its potential anti-tumor activity. JZC01 targeted vascular endothelial growth factor receptor 2 (VEGFR2) and inhibited tumorigenesis ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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