Redefining innate natural antibodies as important contributors to anti-tumor immunity

Myeloid, T, and NK cells are key players in the elimination phase of cancer immunoediting, also referred to as cancer immunosurveillance. However, the role of B cells and NAbs, which are present prior to the encounter with cognate antigens, has been overlooked. One reason is due to the popular use o...

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Autores principales:	Kavita Rawat, Anita Tewari, Madeline J Morrisson, Tor D Wager, Claudia V Jakubzick
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	natural antibodies cancer immunesurveillance neoantigen pDCs Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e99bbf8e0ba34ca585cdaf55ab965b8b
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spelling	oai:doaj.org-article:e99bbf8e0ba34ca585cdaf55ab965b8b2021-11-30T09:57:43ZRedefining innate natural antibodies as important contributors to anti-tumor immunity10.7554/eLife.697132050-084Xe69713https://doaj.org/article/e99bbf8e0ba34ca585cdaf55ab965b8b2021-10-01T00:00:00Zhttps://elifesciences.org/articles/69713https://doaj.org/toc/2050-084XMyeloid, T, and NK cells are key players in the elimination phase of cancer immunoediting, also referred to as cancer immunosurveillance. However, the role of B cells and NAbs, which are present prior to the encounter with cognate antigens, has been overlooked. One reason is due to the popular use of a single B cell-deficient mouse model, muMT mice. Cancer models using muMT mice display a similar tumor burden as their wild-type (WT) counterparts. Empirically, we observe what others have previously reported with muMT mice. However, using two other B cell-deficient mouse models (IgHELMD4 and CD19creDTA), we show a three- to fivefold increase in tumor burden relative to WT mice. In addition, using an unconventional, non-cancer-related, immune neoantigen model where hypoxic conditions and cell clustering are absent, we provide evidence that B cells and their innate, natural antibodies (NAbs) are critical for the detection and elimination of neoantigen-expressing cells. Finally, we find that muMT mice display anti-tumor immunity because of an unexpected compensatory mechanism consisting of significantly enhanced type 1 interferon (IFN)-producing plasmacytoid dendritic cells (pDCs), which recruit a substantial number of NK cells to the tumor microenvironment compared to WT mice. Diminishing this compensatory pDC-IFN-NK cell mechanism revealed that muMT mice develop a three- to fivefold increase in tumor burden compared to WT mice. In summary, our findings suggest that NAbs are part of an early defense against not only microorganisms and dying cells, but precancerous cells as well.Kavita RawatAnita TewariMadeline J MorrissonTor D WagerClaudia V JakubzickeLife Sciences Publications Ltdarticlenatural antibodiescancer immunesurveillanceneoantigenpDCsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	natural antibodies cancer immunesurveillance neoantigen pDCs Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	natural antibodies cancer immunesurveillance neoantigen pDCs Medicine R Science Q Biology (General) QH301-705.5 Kavita Rawat Anita Tewari Madeline J Morrisson Tor D Wager Claudia V Jakubzick Redefining innate natural antibodies as important contributors to anti-tumor immunity
description	Myeloid, T, and NK cells are key players in the elimination phase of cancer immunoediting, also referred to as cancer immunosurveillance. However, the role of B cells and NAbs, which are present prior to the encounter with cognate antigens, has been overlooked. One reason is due to the popular use of a single B cell-deficient mouse model, muMT mice. Cancer models using muMT mice display a similar tumor burden as their wild-type (WT) counterparts. Empirically, we observe what others have previously reported with muMT mice. However, using two other B cell-deficient mouse models (IgHELMD4 and CD19creDTA), we show a three- to fivefold increase in tumor burden relative to WT mice. In addition, using an unconventional, non-cancer-related, immune neoantigen model where hypoxic conditions and cell clustering are absent, we provide evidence that B cells and their innate, natural antibodies (NAbs) are critical for the detection and elimination of neoantigen-expressing cells. Finally, we find that muMT mice display anti-tumor immunity because of an unexpected compensatory mechanism consisting of significantly enhanced type 1 interferon (IFN)-producing plasmacytoid dendritic cells (pDCs), which recruit a substantial number of NK cells to the tumor microenvironment compared to WT mice. Diminishing this compensatory pDC-IFN-NK cell mechanism revealed that muMT mice develop a three- to fivefold increase in tumor burden compared to WT mice. In summary, our findings suggest that NAbs are part of an early defense against not only microorganisms and dying cells, but precancerous cells as well.
format	article
author	Kavita Rawat Anita Tewari Madeline J Morrisson Tor D Wager Claudia V Jakubzick
author_facet	Kavita Rawat Anita Tewari Madeline J Morrisson Tor D Wager Claudia V Jakubzick
author_sort	Kavita Rawat
title	Redefining innate natural antibodies as important contributors to anti-tumor immunity
title_short	Redefining innate natural antibodies as important contributors to anti-tumor immunity
title_full	Redefining innate natural antibodies as important contributors to anti-tumor immunity
title_fullStr	Redefining innate natural antibodies as important contributors to anti-tumor immunity
title_full_unstemmed	Redefining innate natural antibodies as important contributors to anti-tumor immunity
title_sort	redefining innate natural antibodies as important contributors to anti-tumor immunity
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/e99bbf8e0ba34ca585cdaf55ab965b8b
work_keys_str_mv	AT kavitarawat redefininginnatenaturalantibodiesasimportantcontributorstoantitumorimmunity AT anitatewari redefininginnatenaturalantibodiesasimportantcontributorstoantitumorimmunity AT madelinejmorrisson redefininginnatenaturalantibodiesasimportantcontributorstoantitumorimmunity AT tordwager redefininginnatenaturalantibodiesasimportantcontributorstoantitumorimmunity AT claudiavjakubzick redefininginnatenaturalantibodiesasimportantcontributorstoantitumorimmunity
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Redefining innate natural antibodies as important contributors to anti-tumor immunity

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