TY - JOUR TI - Redefining innate natural antibodies as important contributors to anti-tumor immunity AU - Rawat, Kavita AU - Tewari, Anita AU - Morrisson, Madeline J AU - Wager, Tor D AU - Jakubzick, Claudia V A2 - Postovit, Lynne-Marie A2 - Diamond, Betty A2 - Postovit, Lynne-Marie A2 - Reis e Sousa, Caetano VL - 10 PY - 2021 DA - 2021/10/05 SP - e69713 C1 - eLife 2021;10:e69713 DO - 10.7554/eLife.69713 UR - https://doi.org/10.7554/eLife.69713 AB - 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. KW - natural antibodies KW - cancer immunesurveillance KW - neoantigen KW - pDCs JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -