scholarly journals Microwave ablation induces Th1-type immune response with activation of ICOS pathway in early-stage breast cancer

2021 ◽  
Vol 9 (4) ◽  
pp. e002343
Author(s):  
Wenbin Zhou ◽  
Muxin Yu ◽  
Hong Pan ◽  
Wen Qiu ◽  
Hui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Clinical Study ◽  
T Cell ◽  
T Cell Receptor ◽  
Microwave Ablation ◽  
Early Stage ◽  
Local Therapy ◽  
Cell Receptor ◽  
Local Effect

BackgroundDespite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported.MethodsThe clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed.ResultsOf 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor.ConclusionsMWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.

scholarly journals Functional Reprogramming of the Primary Immune Response by T Cell Receptor Antagonism

2004 ◽  
Vol 200 (11) ◽  
pp. 1371-1382 ◽  
Author(s):  
Dipica Haribhai ◽  
Brandon Edwards ◽  
Mary L. Williams ◽  
Calvin B. Williams
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Fate ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Effector Function ◽  
Primary Immune Response ◽  
Cell Homing ◽  
T Cell Homing ◽  
Cell Receptor Antagonism

The T cell receptor must translate modest, quantitative differences in ligand binding kinetics into the qualitatively distinct signals used to determine cell fate. Here, we use mice that express an endogenous T cell receptor (TCR) antagonist and an adoptive transfer system to examine the influence of TCR signal quality on the development of effector function. We show that activation of antigen-specific T cells in the presence of an antagonist results in a functional reprogramming of the primary immune response, marked by altered T cell homing, a failure to develop effector function, and ultimately clonal elimination by apoptosis. Importantly, antagonism does not block cell division, implying that the signals promoting clonal expansion and effector differentiation are distinct.

scholarly journals Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL

2018 ◽  
Vol 7 (6) ◽  
pp. e1432328 ◽  
Author(s):  
Gonzalo Blanco ◽  
Anna Vardi ◽  
Anna Puiggros ◽  
Andrea Gómez-Llonín ◽  
Manuel Muro ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Early Stage ◽  
Cell Receptor ◽  
Receptor Repertoire ◽  
T Cell Receptor Repertoire ◽  
Cell Receptor Repertoire

scholarly journals THER-06. GENOMIC AND IMMUNE CHARACTERIZATION OF TRIPLE NEGATIVE BREAST CANCER BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i11-i12
Author(s):  
Benjamin Vincent ◽  
Maria Sambade ◽  
Shengjie Chai ◽  
Marni Siegel ◽  
Luz Cuaboy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Brain Metastases ◽  
T Cell Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Receptor ◽  
Gene Signature ◽  
Specific Response ◽  
Immune Gene

Abstract INTRODUCTION: Approximately 50% of patients with metastatic triple negative breast cancer (TNBC) will develop brain metastases (BM). Routinely treated with radiotherapy and/or surgery, survival is generally less than one year. There are no approved systemic therapies to treat TNBC BM. We characterized the genomic and immune landscape of TNBC BM to foster the development of effective brain permeable anti-cancer agents, including immunotherapy. EXPERIMENTAL PROCEDURES: A clinically-annotated BCBM biobank of archival tissues was created under IRB approval. DNA (tumor/normal) and RNA (tumor) were extracted from TNBC primaries and BM; whole exome (WES) and RNA sequencing (RNASeq) was performed. Mutations were determined from WES as those co-identified by two variant callers (Strelka|Cadabra). Immune gene signature expression, molecular subtype identification, and T cell receptor repertoires were inferred from RNAseq. RESULTS: 32 TNBC patient tissues (14 primaries, 18 BCBM, 6 primary-BCBM matched), characterized as basal-like by PAM50, were analyzed. Top exome mutation calls included ten genes in ≥19% of BCBMs including TP53, ATM, and PIK3R1, and four genes in ≥18% of primaries including TP53 and PIK3R1. Many immune gene signatures were lower in BM compared to primaries including B cell, dendritic cell, regulatory T cell, and IgG cluster (p< 0.05). A signature of PD-1 inhibition responsiveness was higher in BM compared with primaries (p< 0.05). BCBM T cell receptor repertoires showed higher evenness and lower read count (both p < 0.01) compared to primaries. CONCLUSIONS: TNBC BM compared to primaries that metastasize to the brain show lower immune gene signature expression, higher PD-1 inhibition response signature expression, and T cell receptor repertoire features less characteristic of an active antigen-specific response. Mutations common to TNBC BM and primaries include TP53 and PIK3R1. Given that non-BCBM (i.e. lung and melanoma) show response to checkpoint inhibitors, these findings collectively support further study of immunotherapy for TNBC BM.

scholarly journals Analyzing the Mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening

2020 ◽  
Vol 38 (10) ◽  
pp. 1194-1202 ◽  
Author(s):  
Huang Huang ◽  
Chunlin Wang ◽  
Florian Rubelt ◽  
Thomas J. Scriba ◽  
Mark M. Davis
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Clustering ◽  
Genome Wide

scholarly journals Heteroduplex analysis of T-cell receptor gamma gene rearrangements for diagnosis and monitoring of cutaneous T-cell lymphomas

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3271-3278 ◽  
Author(s):  
M Bottaro ◽  
E Berti ◽  
A Biondi ◽  
N Migone ◽  
L Crosti
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Early Stage ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Heteroduplex Analysis ◽  
Variable Intensity ◽  
T Cell Lymphomas ◽  
Major Clone ◽  
Immunohistochemical Diagnosis

Abstract The possibility to detect markers of T-cell clonality at the T-cell receptor (TCR) beta and gamma loci in skin biopsy samples has proven to be helpful for the often difficult clinical and immunohistochemical diagnosis of cutaneous T-cell lymphoma (CTCL). However, particularly at the early stage of the neoplastic infiltration, an emerging clonal pattern at Southern may be obscured by the germline TCR configuration of the predominant dermal and epidermal cell component. Additionally, multiple TCR gamma rearranged bands of variable intensity are often observed, either in the presence or in the absence of a major clone. To overcome these difficulties, we have investigated the T-lymphocyte clonality in selected patients with variable signs of CTCL by means of heteroduplex analysis of the amplified TCR gamma VJ junctions, separated in nondenaturing polyacrylamide gel. This technique has several advantages over standard Southern blot because it is simple, rapid, not radioactive, and likely more sensitive than other polymerase chain reaction-based procedures. In particular, the cases with uncertain or contradictory TCR beta and gamma patterns were solved by the heteroduplex analysis, showing homoduplex or heteroduplex bands of clonal nature. The direct sequence of the VJ junctions, easily obtained from the homoduplex or heteroduplex bands, allowed us to confirm the same clonal marker in two apparently different skin lesions and in different biopsy samples obtained from the same patients, either at the same or different time points, thus emphasizing the utility of this method in monitoring CTCL clinical progression.

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