14,077 results match your criteria tumor-infiltrating lymphocytes


Resistance Mechanisms to Programmed Cell Death Protein 1 and Programmed Death Ligand 1 inhibitors.

Expert Opin Biol Ther 2021 May 13. Epub 2021 May 13.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: In the past few years, administrating monoclonal humanized antibodies, namely checkpoint inhibitors, against programmed cell death protein 1 (PD-1), and its ligand (PD-L1), has yielded reassuring tumor regression rates. Anti-PD-1/PD-L1 checkpoint inhibitors disrupt the engagement of PD-1 on T-cells and their ligands on tumor or other target cells and reactivate the tumor-specific T infiltrating lymphocytes (TILs), which are mostly in a state of anergy before the PD-1/PD-L1 blockade. However, a limited number of patients initially respond, and the others show a primary (innate) resistance. Read More

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The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer.

Breast Cancer Res Treat 2021 May 13. Epub 2021 May 13.

Cancer Trials Ireland, Dublin, Ireland.

Background: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment.

Methods: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Read More

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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

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Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma.

J Clin Oncol 2021 May 12:JCO2100612. Epub 2021 May 12.

James Graham Brown Cancer Center, University of Louisville, Louisville, KY.

Purpose: Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product. Read More

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Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[F]FDG PET/CT.

Eur J Nucl Med Mol Imaging 2021 May 12. Epub 2021 May 12.

Department of Nuclear Medicine, Peking University First Hospital, Beijing, 100034, China.

Purpose: Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC).

Methods: Ninety patients with newly diagnosed ccRCC who underwent 2-[F]FDG PET/CT prior to surgery were retrospectively reviewed. Read More

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Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression.

Mol Diagn Ther 2021 May 11. Epub 2021 May 11.

Azienda Tutela della Salute Sardegna, Ospedale A. Segni, Ozieri, Italy.

Hormone-receptor positive (HR+) breast cancer (BC) (including the luminal A and the luminal B subtypes) is the most common type of tumor in women diagnosed with early-stage BC (EBC). It represents a highly heterogeneous subgroup that is characterized by different risks of relapse. The aim of this review is to discuss the possible role played by the immune response in predicting this risk, along with the most common clinical and pathological factors and molecular tools that have been developed and are already in use. Read More

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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

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Histogram parameters derived from T1 and T2 weighted images correlate with tumor infiltrating lymphocytes and tumor-stroma ratio in head and neck squamous cell cancer.

Magn Reson Imaging 2021 May 7. Epub 2021 May 7.

Department of Diagnostic and Interventional Radiology, University of Magdeburg, Germany.

Purpose: The present study used histogram analysis values derived from T1- and T2- weighted (w) images to elucidate possible associations with Tumor-infiltrating lymphocytes (TIL) and Vimentin expression in head and neck squamous cell cancer (HNSCC).

Materials And Methods: Overall, 28 patients (n = 8 female patient, 28.6%) with primary HNSCC of different localizations were involved in the study. Read More

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Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors.

Curr Drug Targets 2021 Mar 24. Epub 2021 Mar 24.

Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary.

The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. Read More

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A highly stable multifunctional aptamer for enhancing antitumor immunity against hepatocellular carcinoma by blocking dual immune checkpoints.

Biomater Sci 2021 May 10. Epub 2021 May 10.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China. and Fujian Institute of Research on The Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China.

T-lymphocytes play a potent role in cancer immunotherapy; while, limited tumor infiltrating lymphocytes (TILs) combined with severe immunosuppression always significantly hinder their antitumor immune responses, especially in solid tumors such as hepatocellular carcinoma (HCC). Here, we prepared a highly stable multifunctional aptamer for strengthening antitumor immunity against HCC solid tumors through a dual immune checkpoint blockade of CTLA-4 and PD-L1. The engineered multifunctional aptamer (termed P1/C4-bi-apt) can block both CTLA-4/B7 and PD-1/PD-L1 signaling pathways and thus enhance the antitumor immune responses. Read More

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Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors.

Int J Med Sci 2021 7;18(11):2327-2338. Epub 2021 Apr 7.

Department of General Surgery, the First Affiliated Hospital of Jinan University, Guangzhou 510632, China.

An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors. Read More

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APE1 facilitates PD-L1-mediated progression of laryngeal and hypopharyngeal squamous cell carcinoma.

Int Immunopharmacol 2021 May 6;97:107675. Epub 2021 May 6.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China. Electronic address:

Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) seriously affect the life quality of patients. Nowadays, immunotherapy is widely used in the treatment of cancer. Tumor-infiltrating lymphocytes (TILs), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) play key roles in the immunotherapy of cancer. Read More

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Medulloblastoma recurrence and metastatic spread are independent of colony-stimulating factor 1 receptor signaling and macrophage survival.

J Neurooncol 2021 May 8. Epub 2021 May 8.

Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

Purpose: Tumor infiltration by immunosuppressive myeloid cells or tumor-associated macrophages (TAMs) contributes to tumor progression and metastasis. In contrast to their adult counterparts, higher TAM signatures do not correlate with aggressive tumor behavior in pediatric brain tumors. While prominent TAM infiltrates exist before and after radiation, the degree to which irradiated macrophages and microglia support progression or leptomeningeal metastasis remains unclear. Read More

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ProTICS reveals prognostic impact of tumor infiltrating immune cells in different molecular subtypes.

Brief Bioinform 2021 May 8. Epub 2021 May 8.

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, M5S 3E1, ON, Canada.

Different subtypes of the same cancer often show distinct genomic signatures and require targeted treatments. The differences at the cellular and molecular levels of tumor microenvironment in different cancer subtypes have significant effects on tumor pathogenesis and prognostic outcomes. Although there have been significant researches on the prognostic association of tumor infiltrating lymphocytes in selected histological subtypes, few investigations have systemically reported the prognostic impacts of immune cells in molecular subtypes, as quantified by machine learning approaches on multi-omics datasets. Read More

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Prognostic and therapeutic role of tumor-infiltrating lymphocyte subtypes in breast cancer.

Cancer Metastasis Rev 2021 May 7. Epub 2021 May 7.

PDX Pharmaceuticals, Inc., Portland, OR, USA.

Increased levels of total tumor-infiltrating lymphocytes (TILs) are generally associated with good prognosis in several breast cancer subtypes. Subtypes of TILs impact both tumor cells and immune cells in a variety of different ways, leading to either a pro-tumor or antitumor effect. Tumor-infiltrating CD8 T cells and natural killer (NK) cells perform as effector cells against tumor cells and are associated with better clinical outcome. Read More

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Single-cell profiles and prognostic impact of tumor-infiltrating lymphocytes co-expressing CD39, CD103, and PD-1 in ovarian cancer.

Clin Cancer Res 2021 May 7. Epub 2021 May 7.

Deeley Research Centre, BC Cancer

Purpose: Tumor-infiltrating lymphocytes (TIL) are strongly associated with survival in most cancers; however, the tumor-reactive subset that drives this prognostic effect remains poorly defined. CD39, CD103, and PD-1 have been independently proposed as markers of tumor-reactive CD8+ TIL in various cancers. We evaluated the phenotype, clonality and prognostic significance of TIL expressing various combinations of these markers in high-grade serous ovarian cancer (HGSC), a malignancy in need of more effective immunotherapeutic approaches. Read More

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LC3A positive "stone like structures" are differentially associated with survival outcomes and CD68 macrophage infiltration in patients with lung adenocarcinoma and squamous cell carcinoma.

Lung Cancer 2021 Apr 15. Epub 2021 Apr 15.

Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine and Dentistry, Palacký University, Olomouc, Czech Republic; Faculty of Medicine, University of Ostrava, Czech Republic. Electronic address:

Aims: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression.

Methods: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides. Read More

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HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer.

Cancer Cell Int 2021 May 7;21(1):252. Epub 2021 May 7.

Department of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yingfeng Road No.33, Haizhu District, Guangzhou, Guangdong, China.

Purpose: The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined.

Methods: We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. Read More

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Personalized combination nano-immunotherapy for robust induction and tumor infiltration of CD8 T cells.

Biomaterials 2021 Apr 27;274:120844. Epub 2021 Apr 27.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:

Identification of tumor-specific mutations, called neoantigens, offers new exciting opportunities for personalized cancer immunotherapy. However, it remains challenging to achieve robust induction of neoantigen-specific T cells and drive their infiltration into the tumor microenvironment (TME). Here, we have developed a novel polyethyleneimine (PEI)-based personalized vaccine platform carrying neoantigen peptides and CpG adjuvants in a compact nanoparticle (NP) for their spatio-temporally concerted delivery. Read More

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Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer.

Bioengineered 2021 Dec;12(1):1676-1688

Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu, Sichuan, P.R. China.

Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Read More

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December 2021

A phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (SUBDUE-1, SUB-urothelial DUrvalumab injection-1 study): clinical trial protocol.

BJU Int 2021 May 6. Epub 2021 May 6.

University of Western Australia (UWA) Medical School, University of Western Australia, Perth, WA, Australia.

Objectives: This article presents the clinical trial protocol for a phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (NMIBC), the SUB-urothelial DUrvalumab injection-1 study (SUBDUE-1). The primary objectives of this study are to assess the safety of sub-urothelial injection of durvalumab using patient reported outcome measures and observed local or systemic adverse events. The secondary objectives are to examine the local immunological efficacy of sub-urothelial administration of durvalumab. Read More

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Gene Expression Classifier Reveals Prognostic Osteosarcoma Microenvironment Molecular Subtypes.

Front Immunol 2021 20;12:623762. Epub 2021 Apr 20.

Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Osteosarcoma (OSA) is the most common bone malignancy and displays high heterogeneity of molecular phenotypes. This study aimed to characterize the molecular features of OSA by developing a classification system based on the gene expression profile of the tumor microenvironment. Integrative analysis was performed using specimens and clinical information for OSA patients from the TARGET program. Read More

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Progesterone promotes immunomodulation and tumor development in the murine mammary gland.

J Immunother Cancer 2021 May;9(5)

Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA

Background: Clinical studies have linked usage of progestins (synthetic progesterone [P4]) to breast cancer risk. However, little is understood regarding the role of native P4, signaling through the progesterone receptor (PR), in breast tumor formation. Recently, we reported a link between PR and immune signaling pathways, showing that P4/PR can repress type I interferon signaling pathways. Read More

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Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

Laryngoscope 2021 May 6. Epub 2021 May 6.

Department of Otolaryngology Head and Neck Surgery, Yokohama City University, Yokohama, Kanagawa, Japan.

Objectives/hypothesis: Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate- or high-grade budding scores was investigated as a prognostic marker for occult neck metastases. Read More

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Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high-grade serous ovarian cancer.

Cancer Med 2021 May 5. Epub 2021 May 5.

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Although the association between tumor-infiltrating CD3 T and CD8 T cells and superior survival in high-grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor-infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized measurements in 260 HGSOC from 2 independent cohorts represented in tissue microarray format to determine the localized expression pattern and clinical significance of CD3 T, CD8 T, and CD45RO cells in HGSOC. Different density of spatial localization of CD3 T, CD8 T, and CD45RO cells exhibited heterogeneous association with OS. Read More

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Tumor-associated Stromal Cellular Density as a Predictor of Recurrence and Mortality in Breast Cancer: Results from Ethnically-diverse Study Populations.

Cancer Epidemiol Biomarkers Prev 2021 May 5. Epub 2021 May 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute.

Background: Tumor-associated stroma is comprised of fibroblasts, tumor infiltrating lymphocytes (TILs), macrophages, endothelial, and other cells, that interactively influence tumor progression through inflammation and wound repair. Although gene expression signatures reflecting wound repair predict breast cancer survival, it is unclear whether combined density of tumor-associated stromal cells, a morphological proxy for inflammation and wound repair signatures on routine hematoxylin and eosin (H&E)-stained sections, is of prognostic relevance.

Methods: By applying machine learning to digitized H&E-stained sections for 2,084 breast cancer patients from China (n=596; 24-55years), Poland (n=810; 31-75years), and the United States (n=678; 55-78years), we characterized tumor-associated stromal cellular density (SCD) as the percentage of tumor-stroma that is occupied by nucleated cells. Read More

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Brainstem Infiltration Predicts Survival in Patients With High-grade Gliomas Treated With Chemoradiotherapy.

Anticancer Res 2021 May;41(5):2583-2589

Department of Radiology, Wakayama Medical University, Wakayama, Japan.

Background/aim: High-grade gliomas have a poor prognosis despite standard treatment. The aim of the study was to identify new prognostic factors to select patients who need more intense treatment.

Patients And Methods: Forty-three consecutive patients underwent surgery plus chemoradiotherapy for pathologically diagnosed high-grade gliomas (grade III, IV). Read More

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PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner.

Cancer Treat Res Commun 2021 Apr 23;28:100379. Epub 2021 Apr 23.

Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou 215006, China; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address:

PD-1 immune checkpoint blockade and cytokine IL-33 have shown significant therapeutic effects in tumor immunotherapy. These therapies promote CD8 T cell activation, proliferation, and effector functions. However, there were few research about the combined therapy efficacy. Read More

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T cells expressing receptor recombination/revision machinery are detected in the tumor microenvironment and expanded in genomically over-unstable models.

Cancer Immunol Res 2021 May 3. Epub 2021 May 3.

Tumor Immunology Unit, Department of Health Sciences, University of Palermo

Tumors undergo dynamic immunoediting as part of a process that balances immunological sensing of emerging neoantigens and evasion from immune responses. Tumor-infiltrating lymphocytes (TILs) comprise heterogeneous subsets of peripheral T cells characterized by diverse functional differentiation states and dependence on TCR specificity gained through recombination events during their development. We hypothesized that within the tumor microenvironment (TME), an antigenic milieu and immunological interface, tumor-infiltrating peripheral T cells could re-express key elements of the TCR recombination machinery, namely Rag1 and Rag2 recombinases and Tdt polymerase, as a potential mechanism involved in the revision of TCR specificity. Read More

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PD1/PD-L1 Expressions in Plasmablastic Lymphoma with Clinicopathological Correlation.

Ann Clin Lab Sci 2021 Mar;51(2):174-181

Department of Pathology and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

The activation of the programmed cell death one (PD1)/PD1 ligand (PD-L1) immune checkpoint pathway is a mechanism of immune evasion characterized by the upregulation of PD-L1 expression by tumor cells and by the tumor microenvironment. This activation leads to the inhibition of PD1-positive T cells and to a decrease in the anti-tumor immune response. Plasmablastic lymphoma (PBL) is an aggressive type of large B-cell lymphoma with limited studies on the frequency of PD1 and PD-L1 expressions and their clinical impact. Read More

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