Tumor Cell Repopulation between Cycles of Chemotherapy is Inhibited by Regulatory T- Cell Depletion in a Murine Mesothelioma Model Licun Wu, MD, Zhihong.

Slides:

Advertisements

Similar presentations

Manish R. Patel, DO, Blake A

Advertisements

Nicotinamide Phosphoribosyltransferase: A Potent Therapeutic Target in Non-small Cell Lung Cancer with Epidermal Growth Factor Receptor-Gene Mutation

Third-party Mesenchymal Stem Cells Improved Human Islet Transplantation in a Humanized Diabetic Mouse Model Hao Wu, Di Wen, Ram I Mahato Molecular Therapy

Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome Xiao Li, MD, Liyan Wan, MD, Jian Geng, MD, Chin-Lee.

Foxp3+ Regulatory T Cells and Natural Killer Cells Distinctly Infiltrate Primary Tumors and Draining Lymph Nodes in Pulmonary Adenocarcinoma Thomas Schneider,

Temsirolimus Inhibits Malignant Pleural Mesothelioma Growth In Vitro and In Vivo: Synergism with Chemotherapy Mir Alireza Hoda, MD, Amir Mohamed, BSc,

Antitumor Efficacy of the Anti-Interleukin-6 (IL-6) Antibody Siltuximab in Mouse Xenograft Models of Lung Cancer Lanxi Song, MS, Matthew A. Smith, PhD,

Yunguang Sun, PhD, Luigi Moretti, MD, Nicholas J

Manish R. Patel, DO, Blake A

Successful Immunotherapy against a Transplantable Mouse Squamous Lung Carcinoma with Anti–PD-1 and Anti-CD137 Monoclonal Antibodies Arantza Azpilikueta,

Volume 33, Issue 3, Pages (September 2010)

Volume 78, Issue 11, Pages (December 2010)

Juyang Kim, Wongyoung Kim, Hyun J. Kim, Sohye Park, Hyun-A

Complexes of trophoblastic peptides and heat shock protein 70 as a novel contraceptive vaccine in a mouse model Mei Han, Yuan Yao, Wangjiang Zeng, Yanfang.

Volume 5, Issue 2, Pages (August 2009)

Volume 141, Issue 1, Pages e1 (July 2011)

Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer by Ou Cao, Eric Dobrzynski,

Tatsukuni Ohno, Yuta Kondo, Chenyang Zhang, Siwen Kang, Miyuki Azuma

Volume 135, Issue 6, Pages (December 2008)

Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome Xiao Li, MD, Liyan Wan, MD, Jian Geng, MD, Chin-Lee.

Activated glycoprotein A repetitions predominant (GARP)–expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice

Volume 8, Issue 5, Pages (May 2017)

Systemic administration of attenuated Salmonella choleraesuis in combination with cisplatin for cancer therapy Che-Hsin Lee, Chao-Liang Wu, Yun-Sheng.

Pulmonary Fibroblasts Induce Epithelial Mesenchymal Transition and Some Characteristics of Stem Cells in Non-Small Cell Lung Cancer Yasushi Shintani,

Combining the Multitargeted Tyrosine Kinase Inhibitor Vandetanib with the Antiestrogen Fulvestrant Enhances Its Antitumor Effect in Non-small Cell Lung.

Early Tumor-Infiltrating Dendritic Cells Change their Characteristics Drastically in Association with Murine Melanoma Progression Takeshi Nakahara, Junna.

Foxp3+ Regulatory T Cells and Natural Killer Cells Distinctly Infiltrate Primary Tumors and Draining Lymph Nodes in Pulmonary Adenocarcinoma Thomas Schneider,

Volume 140, Issue 7, Pages (June 2011)

Anti-Vascular Endothelial Growth Factor Treatment in Combination with Chemotherapy Delays Hematopoietic Recovery Due to Decreased Proliferation of Bone.

Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non– Small Cell Lung Cancer Xenograft Models Josephine Hai, PhD, Shingo Sakashita,

Volume 143, Issue 1, Pages (July 2012)

Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice Jörg.

Volume 138, Issue 2, Pages (February 2010)

Immuno-gene therapy with interferon-β before surgical debulking delays recurrence and improves survival in a murine model of malignant mesothelioma Robert.

Volume 33, Issue 3, Pages (September 2010)

by Adrienne Sallets, Sophie Robinson, Adel Kardosh, and Ronald Levy

Third-party Mesenchymal Stem Cells Improved Human Islet Transplantation in a Humanized Diabetic Mouse Model Hao Wu, Di Wen, Ram I Mahato Molecular Therapy

Volume 26, Issue 2, Pages (February 2018)

Volume 16, Issue 3, Pages (September 2009)

Apelin Expression in Human Non-small Cell Lung Cancer: Role in Angiogenesis and Prognosis Judit Berta, MS, Istvan Kenessey, MD, Judit Dobos, PhD, Jozsef.

Superior Suppressive Capacity of Skin Tregs Compared with Lung Tregs in a Model of Epicutaneous Priming Subhashree Mahapatra, Melanie Albrecht, Abdul.

Volume 28, Issue 6, Pages (June 2008)

Volume 18, Issue 9, Pages (September 2010)

Shisuo Du, MD, Lin Zhou, MD, Gregory S

Suppression of Murine Colitis and its Associated Cancer by Carcinoembryonic Antigen- Specific Regulatory T Cells Dan Blat, Ehud Zigmond, Zoya Alteber,

Interleukin-18 and the Costimulatory Molecule B7-1 Have a Synergistic Anti-Tumor Effect on Murine Melanoma; Implication of Combined Immunotherapy for.

Triple Inhibition of EGFR, Met, and VEGF Suppresses Regrowth of HGF-Triggered, Erlotinib-Resistant Lung Cancer Harboring an EGFR Mutation Junya Nakade,

Wei-Yun Lai, Bo-Tsang Huang, Jen-Wei Wang, Pei-Ying Lin, Pan-Chyr Yang

Nicotinamide Phosphoribosyltransferase: A Potent Therapeutic Target in Non-small Cell Lung Cancer with Epidermal Growth Factor Receptor-Gene Mutation

Donor antigen-presenting cells regulate T-cell expansion and antitumor activity after allogeneic bone marrow transplantation Jian-Ming Li, Edmund K.

Volume 17, Issue 2, Pages (February 2009)

Volume 22, Issue 1, Pages (January 2014)

Agatha Schwarz, Anika Bruhs, Thomas Schwarz

Volume 35, Issue 2, Pages (August 2011)

Volume 20, Issue 5, Pages (May 2012)

Chie Kudo-Saito, Hiromi Shirako, Tadashi Takeuchi, Yutaka Kawakami

In Vivo Expansion of Regulatory T cells With IL-2/IL-2 mAb Complexes Prevents Anti- factor VIII Immune Responses in Hemophilia A Mice Treated With Factor.

CD8+ T cells were immunomodulated and required for the efficacy of anti–4-1BB/anti–PD-1 combination treatment. CD8+ T cells were immunomodulated and required.

Javed Mohammed, Andrew Ryscavage, Rolando Perez-Lorenzo, Andrew J

Volume 26, Issue 1, Pages (January 2018)

Volume 28, Issue 5, Pages (May 2008)

Volume 17, Issue 5, Pages (May 2009)

Sindbis Viral Vectors Transiently Deliver Tumor-associated Antigens to Lymph Nodes and Elicit Diversified Antitumor CD8+ T-cell Immunity Tomer Granot,

Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: Role of eosinophils, IL-5, eotaxin, and IL-13 Seok-Yong.

Volume 26, Issue 4, Pages (April 2018)

Volume 8, Issue 3, Pages (August 2014)

Local Inhibition of Complement Improves Mesenchymal Stem Cell Viability and Function After Administration Yan Li, John Fung, Feng Lin Molecular Therapy

Genetic Targeting of the Active Transcription Factor XBP1s to Dendritic Cells Potentiates Vaccine-induced Prophylactic and Therapeutic Antitumor Immunity

Volume 13, Issue 11, Pages (December 2015)

Volume 37, Issue 2, Pages (August 2012)

Presentation transcript:

Tumor Cell Repopulation between Cycles of Chemotherapy is Inhibited by Regulatory T- Cell Depletion in a Murine Mesothelioma Model Licun Wu, MD, Zhihong Yun, MSc, Tetsuzo Tagawa, MD, PhD, Katrina Rey-McIntyre, BSc, Masaki Anraku, MD, MSc, Marc de Perrot, MD, MSc Journal of Thoracic Oncology Volume 6, Issue 9, Pages 1578-1586 (September 2011) DOI: 10.1097/JTO.0b013e3182208ee0 Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Murine mesothelioma AC29 cells were injected subcutaneously (SC) into the flanks of CBA mice. Once tumors are palpable (approximately 5 mm in diameter at day 4 ± 1 posttumor cell injection), treatment was initiated as follows: no treatment, cisplatin (Cis) alone, cyclophosphamide alone, PC61 alone, cisplatin combined with Treg depletion by CD25 monoclonal antibody PC61 (CPC), or cisplatin combined with low dose of cyclophosphamide (CCY) (A). Tumor growth delay after both combination treatments with PC61 or CY following cisplatin was achieved (B and C). Each group contained at least five mice. Tumor growth curves after treatment shown are the averages of three experiments. *p < 0.05, compared with controls. Journal of Thoracic Oncology 2011 6, 1578-1586DOI: (10.1097/JTO.0b013e3182208ee0) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Tumor cell repopulation between cycles of chemotherapy was inhibited by Treg cell depletion with anti-CD25 monoclonal antibody PC61. Single tumor cells were prepared at day 21 after treatment. BrdU was injected intraperitoneally (IP) 3 hours before animals were killed. BrdU labeling index of tumor cells was determined by flow cytometry. Representative data generated from five tumors of each group on day 21 showing tumor cell repopulation (A). Nuclear immunostaining of BrdU incorporation and quantification of highlighted positive nuclear areas were shown in (B) and (C), respectively. Gene expression of internal proliferation markerKi67 was evaluated by real-time reverse-transcribed polymerase chain reaction (RT-PCR) (D). Columns, mean; bars, SEM. *p < 0.05, compared with controls. Journal of Thoracic Oncology 2011 6, 1578-1586DOI: (10.1097/JTO.0b013e3182208ee0) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Populations of T-cell subsets 7 days after completing three cycles of chemotherapy. Single cells from the spleen, draining lymph node, and peripheral blood were prepared and stained according to the methods mentioned earlier in the text. Treg cells were identified by positive staining of CD4+CD25+FoxP3+. The proportion of Treg cells was analyzed based on positivity of the above three markers, and all p values are less than 0.05 in the CPC group (A). Total CD4+ T cells and CD8+ T cells were determined by the proportion of CD3+CD4+ and CD3+CD8+ cells by flow cytometry, and there was no significant difference as shown in (B). Each group had at least five mice, and the experiment was repeated twice. Columns, mean; bars, SEM. *p < 0.05, compared with controls. Journal of Thoracic Oncology 2011 6, 1578-1586DOI: (10.1097/JTO.0b013e3182208ee0) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Populations of T-cell subsets 7 days after completing three cycles of chemotherapy. Single cells from the tumor tissues were prepared and stained according to the methods. Treg cells were identified by positive staining of CD4+CD25+, CD4+FoxP3+, and CD4+CD25+FoxP3+. The proportion of Treg cells was analyzed based on positivity of the above three markers (A). Total CD4+ T cells and CD8+ T cells were determined by the proportion of CD3+CD4+ and CD3+CD8+ cells by flow cytometry (B). (Each group had at least five mice, and the experiment was repeated twice). Columns, mean; bars, SEM. *p < 0.05, compared with controls. Journal of Thoracic Oncology 2011 6, 1578-1586DOI: (10.1097/JTO.0b013e3182208ee0) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 5 Specific cell killing of splenocytes derived from AC29 tumor-bearing mice treated with cisplatin (Cis) or PC61 alone, combination of cisplatin with PC61 (CPC) or cyclophosphamide (CCY), and naive mice were also included as control. This experiment was repeated at least twice. *p < 0.05, compared with naive mice. Journal of Thoracic Oncology 2011 6, 1578-1586DOI: (10.1097/JTO.0b013e3182208ee0) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 6 Cytokine production in tumor tissue 7 days after completing treatment by enzyme-linked immunosorbent assay (ELISA) (top panel, A), and gene expression of activated T-cell-related cytokines was shown in reverse-transcribed polymerase chain reaction (RT-PCR) results (bottom panel, B). All these experiments were repeated twice. Columns, mean; bars, SEM. *p < 0.05, compared with controls. Journal of Thoracic Oncology 2011 6, 1578-1586DOI: (10.1097/JTO.0b013e3182208ee0) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions