scholarly journals Vertebral-specific activation of the CX3CL1/ICAM-1 signaling network mediates non-small-cell lung cancer spinal metastasis by engaging tumor cell-vertebral bone marrow endothelial cell interactions

Theranostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 4770-4789
Author(s):  
Ketao Wang ◽  
Libo Jiang ◽  
Annan Hu ◽  
Chi Sun ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Endothelial Cell ◽  
Tumor Cell ◽  
Spinal Metastasis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Vertebral Bone ◽  
Bone Marrow Endothelial Cell ◽  
Vertebral Bone Marrow

154 Marrow-infiltrating lymphocytes (MILs): A novel adoptive immunotherapy for hematological and solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A168-A168
Author(s):  
Eric Lutz ◽  
Lakshmi Rudraraju ◽  
Elizabeth DeOliveira ◽  
Amanda Seiz ◽  
Monil Shah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cells ◽  
Memory T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Blood Samples ◽  
Infiltrating Lymphocytes

BackgroundMarrow infiltrating lymphocytes (MILsTM) are the product of activating and expanding bone marrow T cells.1 The bone marrow is a specialized niche in the immune system enriched for antigen-experienced, memory T cells. In patients with multiple myeloma and other hematological malignancies that relapse post-transplant, MILs have been shown to contain tumor antigen-specific T cells and adoptive cell therapy (ACT) using MILs has demonstrated antitumor activity.2 3 The bone marrow has been shown to harbor tumor-antigen specific T cells in patients with melanoma,4 5 glioblastoma,6 breast,7 non-small-cell lung8 and pancreatic cancers.9 Here, we sought to determine if tumor-specific MILs could be expanded from the bone marrow of patients with a range of different solid tumors.MethodsBone marrow and blood samples were collected from patients with advanced and metastatic cancers. To date, samples have been collected from a minimum of four patients with non-small cell lung cancer (NSCLC), prostate cancer, head and neck cancer, glioblastoma, and breast cancer. Samples from patients with multiple myeloma were used as a reference control. Utilizing a 10-day proprietary process, MILs and peripheral blood lymphocytes (PBLs) were activated and expanded from patient bone marrow and blood samples, respectively. T cell lineage-specific markers (CD3, CD4 and CD8) were characterized by flow cytometry pre- and post-expansion.Tumor-specific T cells were quantitated in expanded MILs and PBLs using a previously described cytokine-secretion assay [2]. Briefly, autologous antigen-presenting cells (APCs) were pulsed with lysates from allogeneic cancer cell lines and co-cultured with activated MILs or PBLs. APCs pulsed with irrelevant mis-matched cancer cell line lysates or media alone were used as negative controls. Tumor-specific T cells were defined as the IFNgamma-producing population by flow cytometry.ResultsMILs were successfully expanded from all patient bone marrow samples tested, regardless of tumor type. Cytokine-producing tumor-specific CD4+ and CD8+ T cells were detected in each of the expanded MILs. In contrast, tumor-specific T cells were not detected in any of the matched activated and expanded PBLs.ConclusionsMILs have been successfully grown for all solid tumor types evaluated, including NSCLC, prostate, head and neck, glioblastoma and breast cancer. Clinical studies have been completed in patients with multiple myeloma and other hematological cancers. 2 3 A phase IIa trial to evaluate MILs in combination with a checkpoint inhibitor is underway in patients with anti-PD1/PDL1-refractory NSCLC (ClinicalTrials.gov Identifier: NCT04069936). The preclinical data presented herein demonstrate that expanding MILs is feasible. MILs-based therapies hold therapeutic promise across a wide range of tumor indications.Ethics ApprovalThis study was approved by each participating instituion’s IRB.ReferencesBorrello I and Noonan KA. Marrow-Infiltrating Lymphocytes - Role in Biology and Cancer Therapy. Front Immunol 2016 March 30; 7(112)Noonan KA, Huff CA, Davis J, et al. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci. Transl. Med 2015;7:288ra78.Biavati L, Noonan K, Luznik L, Borrello I. Activated allogeneic donor-derived marrow-infiltrating lymphocytes display measurable in vitro antitumor activity. J Immunother 2019 Apr;42(3):73–80.Müller-Berghaus J, Ehlert K, Ugurel S, et al. Melanoma-reactive T cells in the bone marrow of melanoma patients: association with disease stage and disease duration. Cancer Res 2006;66(12):5997–6001.Letsch A, Keilholz U, Assfalg G, et al., Bone marrow contains melanoma-reactive CD8+ effector T Cells and, compared with peripheral blood, enriched numbers of melanoma-reactive CD8+ memory T cells. Cancer Res 2003 Sep 1;63(17):5582–5586.Chongsathidkiet P, Jackson C, Koyama S, et al., Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nature Medicine 2018 Aug 13; 24:1459–1468.Feuerer M, Rocha M, Bai L, et al. Enrichment of memory T cells and other profound immunological changes in the bone marrow from untreated breast cancer patients. Int J Cancer 2001; 92(1):96–105.Safi S, Yamauchi Y, Stamova S, et al. Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer. Oncoimmunology 2019;8(12):e1671762.Schmitz-Winnenthal FH, Volk C, Z’Graggen K, et al. High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients. Cancer Res 2005;65(21):10079–87.

901 Single disseminated tumor cells in bone marrow and PBSC in patients with small cell lung cancer

Lung Cancer ◽  
1997 ◽  
Vol 18 ◽  
pp. 229-230
Author(s):  
U. Seifart ◽  
S. Henrich ◽  
G. Jaques ◽  
C. Loechelt ◽  
A. Wachtel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Disseminated Tumor Cells ◽  
Small Cell ◽  
Small Cell Lung

Abstract 596: Single circulating tumor cell enumeration and targeted sequencing in non-small cell lung cancer

2021 ◽  
Author(s):  
Mouadh Barbirou ◽  
Yariswamy Manjunath ◽  
Amanda Miller ◽  
Arturo Ramirez ◽  
Nolan Ericson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Circulating Tumor Cell ◽  
Small Cell ◽  
Targeted Sequencing ◽  
Small Cell Lung ◽  
Cell Enumeration

scholarly journals Intramedullary thoracic spinal metastasis from small-cell lung cancer

2013 ◽  
Vol 79 (3-4) ◽  
Author(s):  
S. Katsenos ◽  
M. Nikolopoulou
Keyword(s):  
Lung Cancer ◽  
Spinal Cord ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Spinal Metastasis ◽  
Small Cell ◽  
Mediastinal Lymphadenopathy ◽  
Small Cell Lung ◽  
Intramedullary Spinal Cord ◽  
Thoracic Spinal

Intramedullary thoracic spinal metastasis from small-cell lung cancer. S. Katsenos, M. Nikolopoulou. Lung cancer with intramedullary spinal cord metastasis (ISCM) is a rare event exhibiting dismal prognosis. In the present paper, we describe a 74-year-old male who developed bilateral leg weakness with associated backache and non-productive cough. Chest imaging evaluation demonstrated pronounced bilateral mediastinal lymphadenopathy and a nodular opacity in the right lower lobe. The patient was diagnosed with small cell lung cancer through bronchoscopic procedures. Magnetic resonance imaging of the spinal cord with contrast-enhancement revealed an intramedullary lesion consistent with metastasis at the T5-T6 level. Despite chemotherapy and thoracic spine radiotherapy, he eventually succumbed to the disease 3 months after diagnosis. A brief overview of the current literature is also provided laying emphasis on the therapeutic strategies of this unusual extrathoracic metastatic disease.

Apoptotic tumor-cell death in response to cell proliferation is influenced by p53 status in resected non-small cell lung cancer

Lung Cancer ◽  
2002 ◽  
Vol 36 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Fumihiro Tanaka ◽  
Tetsuya Takata ◽  
Tomoko Yamada ◽  
Kazuhiro Yanagihara ◽  
Yosuke Otake ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Cell Death ◽  
Apoptotic Tumor Cell ◽  
P53 Status

scholarly journals OTHR-07. Systematic Review and Meta-analysis of Lung Cancer Brain Metastasis and Primary Tumor PD-L1 Expression Discordance

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii15-iii16
Author(s):  
Raees Tonse ◽  
Muni Rubens ◽  
Haley Appel ◽  
Martin C Tom ◽  
Matthew D Hall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Small Cell ◽  
Receptor Expression ◽  
Small Cell Lung

Abstract Background Novel immunotherapeutic strategies, such as those targeting the PD-1/PD-L1 axis, are promising in patients with metastatic lung cancer and are often administered when tumors show PD-L1 positivity. The objective of this study was to analyze PD-L1 receptor discordance in tumor cell between the primary tumor and lung cancer brain metastasis (LCBM). Methods A systematic review of series published prior to April 2021 obtained from the Medline database of biopsied or resected LCBM evaluating PD-L1 discordance was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates. Results Six full-text articles (n=247 patients) with a median of 32 patients in each study (range: 24–73 patients) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases. The majority of patients (81%) were smokers, with 67% non-small cell lung cancer and 33% small cell lung cancer. The pooled estimate for overall PD-LI receptor concordance between primary and LCBM was 76% (95% CI: 52%-90). The positivity rate varied when analyzed by various cutoff levels of PD-L1 expression; for <1% expression, it was 41% (95% CI: 22%-62%) for primary vs. 58% (95% CI: 35%-78%) for LCBM; for PD-L1 expression of 1–50%, it was 24% (95% CI: 13%-40%) vs. 19% (95% CI: 10%-33%); and for PD-L1 >50% it was 12% (95% CI: 4%-33%) vs. 21% (95% CI: 14%-29%) (p=0.425). The pooled estimate for overall PD-LI receptor discordance between primary and LCBM was 17% (95% CI: 10%-27%). Meta-regression analysis showed that age, sex, smoking status, and histology were not associated with PD-LI receptor discordance. Conclusions PD-L1 status discordance in tumor cell occurs in approximately 20% of LCBM, with the greatest discordance in the <1% expression category. Awareness of this discordance is important for the selection of immune checkpoint inhibitor therapy as well as in the analysis of patterns of failures.

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