HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions
Pleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namel...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.02027/full |
| _version_ | 1828777484760383488 |
|---|---|
| author | Adam C. Soloff Adam C. Soloff Katherine E. Jones Amy A. Powers Pranav Murthy Yue Wang Yue Wang Kira L. Russell Miranda Byrne-Steele Amanda W. Lund Jian-Min Yuan Jian-Min Yuan Sara E. Monaco Jian Han Rajeev Dhupar Rajeev Dhupar Michael T. Lotze Michael T. Lotze Michael T. Lotze |
| author_facet | Adam C. Soloff Adam C. Soloff Katherine E. Jones Amy A. Powers Pranav Murthy Yue Wang Yue Wang Kira L. Russell Miranda Byrne-Steele Amanda W. Lund Jian-Min Yuan Jian-Min Yuan Sara E. Monaco Jian Han Rajeev Dhupar Rajeev Dhupar Michael T. Lotze Michael T. Lotze Michael T. Lotze |
| author_sort | Adam C. Soloff |
| collection | DOAJ |
| description | Pleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namely that the lymphatics are only passive vessels, carrying antigenic fluid to secondary lymphoid sites. Rather, lymphatic vessels can be a selective barrier, efficiently coordinating egress of immune cells and factors within tissues, limiting tumor spread and immune pathology. An alternative explanation, offered here, is that damage associated molecular pattern molecules, released in excess, maintain a local milieu associated with recruitment and retention of immune cells associated with failed lymphatic clearance and functional lymphatic obstruction. We found that levels of high mobility group box 1 (HMGB1) were equally elevated in both benign and malignant pleural effusions (MPEs) and that limited diversity of T cell receptor expressing gamma and delta chain were inversely associated with these levels in MPEs. Acellular fluid from MPEs enhanced γδ T cell proliferation in vitro, while inhibiting cytokine production from γδ T cells and monocytes as well as restricting monocyte chemotaxis. Novel therapeutic strategies, targeting HMGB1 and its neutralization in such effusions as well as direct delivery of immune cells into the pleural space to reconstitute normal physiology should be considered. |
| first_indexed | 2024-12-11T16:21:33Z |
| format | Article |
| id | doaj.art-5a91f8982a8f4d58a0286b73dfb64139 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T16:21:33Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5a91f8982a8f4d58a0286b73dfb641392022-12-22T00:58:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.02027532090HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural EffusionsAdam C. Soloff0Adam C. Soloff1Katherine E. Jones2Amy A. Powers3Pranav Murthy4Yue Wang5Yue Wang6Kira L. Russell7Miranda Byrne-Steele8Amanda W. Lund9Jian-Min Yuan10Jian-Min Yuan11Sara E. Monaco12Jian Han13Rajeev Dhupar14Rajeev Dhupar15Michael T. Lotze16Michael T. Lotze17Michael T. Lotze18Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, United StatesDepartment of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Surgery, Division of Surgical Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Surgery, Division of Surgical Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartments of Immunology and Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Surgery, Division of Surgical Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesiRepertoire, Inc., Huntsville, AL, United StatesDepartment of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, United StatesDivision of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, Pittsburgh, PA, United StatesDepartment of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesiRepertoire, Inc., Huntsville, AL, United StatesDepartment of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States0Surgical Services Division, VA Pittsburgh Healthcare System, Pittsburgh, PA, United StatesCancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, United StatesDepartment of Surgery, Division of Surgical Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartments of Immunology and Bioengineering, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesPleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namely that the lymphatics are only passive vessels, carrying antigenic fluid to secondary lymphoid sites. Rather, lymphatic vessels can be a selective barrier, efficiently coordinating egress of immune cells and factors within tissues, limiting tumor spread and immune pathology. An alternative explanation, offered here, is that damage associated molecular pattern molecules, released in excess, maintain a local milieu associated with recruitment and retention of immune cells associated with failed lymphatic clearance and functional lymphatic obstruction. We found that levels of high mobility group box 1 (HMGB1) were equally elevated in both benign and malignant pleural effusions (MPEs) and that limited diversity of T cell receptor expressing gamma and delta chain were inversely associated with these levels in MPEs. Acellular fluid from MPEs enhanced γδ T cell proliferation in vitro, while inhibiting cytokine production from γδ T cells and monocytes as well as restricting monocyte chemotaxis. Novel therapeutic strategies, targeting HMGB1 and its neutralization in such effusions as well as direct delivery of immune cells into the pleural space to reconstitute normal physiology should be considered.https://www.frontiersin.org/article/10.3389/fimmu.2020.02027/fullHMGB1malignant pleural effusionsbenign pleural effusionsimmune repertoiretumor immunologyγδ T cells |
| spellingShingle | Adam C. Soloff Adam C. Soloff Katherine E. Jones Amy A. Powers Pranav Murthy Yue Wang Yue Wang Kira L. Russell Miranda Byrne-Steele Amanda W. Lund Jian-Min Yuan Jian-Min Yuan Sara E. Monaco Jian Han Rajeev Dhupar Rajeev Dhupar Michael T. Lotze Michael T. Lotze Michael T. Lotze HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions Frontiers in Immunology HMGB1 malignant pleural effusions benign pleural effusions immune repertoire tumor immunology γδ T cells |
| title | HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions |
| title_full | HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions |
| title_fullStr | HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions |
| title_full_unstemmed | HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions |
| title_short | HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions |
| title_sort | hmgb1 promotes myeloid egress and limits lymphatic clearance of malignant pleural effusions |
| topic | HMGB1 malignant pleural effusions benign pleural effusions immune repertoire tumor immunology γδ T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.02027/full |
| work_keys_str_mv | AT adamcsoloff hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT adamcsoloff hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT katherineejones hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT amyapowers hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT pranavmurthy hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT yuewang hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT yuewang hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT kiralrussell hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT mirandabyrnesteele hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT amandawlund hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT jianminyuan hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT jianminyuan hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT saraemonaco hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT jianhan hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT rajeevdhupar hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT rajeevdhupar hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT michaeltlotze hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT michaeltlotze hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions AT michaeltlotze hmgb1promotesmyeloidegressandlimitslymphaticclearanceofmalignantpleuraleffusions |