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L2pB1 Cells Contribute to Tumor Growth Inhibition

Natural IgM (nIgM) antibodies play critical roles in cancer immunosurveillance. However, the role of B-1 B cells, the lymphocytes that produce nIgM, remains to be elucidated. L2pB1 cells, a subpopulation of B-1 B cells, have a unique poly-self-reactive nIgM repertoire and are capable of phagocytosis...

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Autores principales: Shibad, Varuna, Bootwala, Ali, Mao, Changchuin, Bader, Hanna, Vo, Hung, Landesman-Bollag, Esther, Guo, Conrad, Rubio, Angel, Near, Richard, Gao, Wenda, Challa, Sreekar, Chukka, Vennela, Gao, Jeffrey, Kelly, Avery, Landesman, Tamar, VanHelene, Tyler, Zhong, Xuemei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495424/
https://www.ncbi.nlm.nih.gov/pubmed/34630396
http://dx.doi.org/10.3389/fimmu.2021.722451
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author Shibad, Varuna
Bootwala, Ali
Mao, Changchuin
Bader, Hanna
Vo, Hung
Landesman-Bollag, Esther
Guo, Conrad
Rubio, Angel
Near, Richard
Gao, Wenda
Challa, Sreekar
Chukka, Vennela
Gao, Jeffrey
Kelly, Avery
Landesman, Tamar
VanHelene, Tyler
Zhong, Xuemei
author_facet Shibad, Varuna
Bootwala, Ali
Mao, Changchuin
Bader, Hanna
Vo, Hung
Landesman-Bollag, Esther
Guo, Conrad
Rubio, Angel
Near, Richard
Gao, Wenda
Challa, Sreekar
Chukka, Vennela
Gao, Jeffrey
Kelly, Avery
Landesman, Tamar
VanHelene, Tyler
Zhong, Xuemei
author_sort Shibad, Varuna
collection PubMed
description Natural IgM (nIgM) antibodies play critical roles in cancer immunosurveillance. However, the role of B-1 B cells, the lymphocytes that produce nIgM, remains to be elucidated. L2pB1 cells, a subpopulation of B-1 B cells, have a unique poly-self-reactive nIgM repertoire and are capable of phagocytosis, potent antigen presentation, and immunomodulation. Using an inducible knock-in and knockout mouse model, we investigated the effect of the loss of L2pB1 cells in a B16F10 melanoma model. Our results show active tumor infiltration of L2pB1 cells in wild type mice, and conversely, depletion of L2pB1 cells results in larger tumor mass and increased angiogenesis. In vitro analysis revealed that L2pB1 cells contribute to the growth inhibition of melanoma cells in both 2D cell culture and 3D tumor spheroids. Similar effects were observed in an MC38 murine colon cancer model. Moreover, our data suggest that one of the ways that L2pB1 cells can induce tumor cell death is via lipoptosis. Lastly, we tested whether L2pB1 cell-derived monoclonal nIgM antibodies can specifically recognize tumor spheroids. Nine of the 28 nIgM-secreting L2pB1 clones demonstrated specific binding to tumor spheroids but did not bind control murine embryonic fibroblasts. Our study provides evidence that L2pB1 cells contribute to cancer immunity through their unique nIgM repertoire, tumor recognition, and lipoptosis. Taken together, because of their ability to recognize common features of tumors that are independent of genetic mutations, L2pB1 cells and their nIgM could be potential candidates for cancer treatment that can overcome tumor heterogeneity-associated drug resistance.
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spelling pubmed-84954242021-10-08 L2pB1 Cells Contribute to Tumor Growth Inhibition Shibad, Varuna Bootwala, Ali Mao, Changchuin Bader, Hanna Vo, Hung Landesman-Bollag, Esther Guo, Conrad Rubio, Angel Near, Richard Gao, Wenda Challa, Sreekar Chukka, Vennela Gao, Jeffrey Kelly, Avery Landesman, Tamar VanHelene, Tyler Zhong, Xuemei Front Immunol Immunology Natural IgM (nIgM) antibodies play critical roles in cancer immunosurveillance. However, the role of B-1 B cells, the lymphocytes that produce nIgM, remains to be elucidated. L2pB1 cells, a subpopulation of B-1 B cells, have a unique poly-self-reactive nIgM repertoire and are capable of phagocytosis, potent antigen presentation, and immunomodulation. Using an inducible knock-in and knockout mouse model, we investigated the effect of the loss of L2pB1 cells in a B16F10 melanoma model. Our results show active tumor infiltration of L2pB1 cells in wild type mice, and conversely, depletion of L2pB1 cells results in larger tumor mass and increased angiogenesis. In vitro analysis revealed that L2pB1 cells contribute to the growth inhibition of melanoma cells in both 2D cell culture and 3D tumor spheroids. Similar effects were observed in an MC38 murine colon cancer model. Moreover, our data suggest that one of the ways that L2pB1 cells can induce tumor cell death is via lipoptosis. Lastly, we tested whether L2pB1 cell-derived monoclonal nIgM antibodies can specifically recognize tumor spheroids. Nine of the 28 nIgM-secreting L2pB1 clones demonstrated specific binding to tumor spheroids but did not bind control murine embryonic fibroblasts. Our study provides evidence that L2pB1 cells contribute to cancer immunity through their unique nIgM repertoire, tumor recognition, and lipoptosis. Taken together, because of their ability to recognize common features of tumors that are independent of genetic mutations, L2pB1 cells and their nIgM could be potential candidates for cancer treatment that can overcome tumor heterogeneity-associated drug resistance. Frontiers Media S.A. 2021-09-23 /pmc/articles/PMC8495424/ /pubmed/34630396 http://dx.doi.org/10.3389/fimmu.2021.722451 Text en Copyright © 2021 Shibad, Bootwala, Mao, Bader, Vo, Landesman-Bollag, Guo, Rubio, Near, Gao, Challa, Chukka, Gao, Kelly, Landesman, VanHelene and Zhong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Shibad, Varuna
Bootwala, Ali
Mao, Changchuin
Bader, Hanna
Vo, Hung
Landesman-Bollag, Esther
Guo, Conrad
Rubio, Angel
Near, Richard
Gao, Wenda
Challa, Sreekar
Chukka, Vennela
Gao, Jeffrey
Kelly, Avery
Landesman, Tamar
VanHelene, Tyler
Zhong, Xuemei
L2pB1 Cells Contribute to Tumor Growth Inhibition
title L2pB1 Cells Contribute to Tumor Growth Inhibition
title_full L2pB1 Cells Contribute to Tumor Growth Inhibition
title_fullStr L2pB1 Cells Contribute to Tumor Growth Inhibition
title_full_unstemmed L2pB1 Cells Contribute to Tumor Growth Inhibition
title_short L2pB1 Cells Contribute to Tumor Growth Inhibition
title_sort l2pb1 cells contribute to tumor growth inhibition
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495424/
https://www.ncbi.nlm.nih.gov/pubmed/34630396
http://dx.doi.org/10.3389/fimmu.2021.722451
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