Author Correction: Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy

Correia, Ana Luísa; Guimaraes, Joao C.; Maur, Priska Auf der; Silva, Duvini De; Trefny, Marcel P.; Okamoto, Ryoko; Bruno, Sandro; Schmidt, Alexander; Mertz, Kirsten D.; Volkmann, Katrin; Terracciano, Luigi; Zippelius, Alfred; Vetter, Marcus; Kurzeder, Christian; Weber, Walter; Bentires‐Alj, Mohamed

doi:10.1038/s41586-021-04104-y

Cited by 5 publications

(4 citation statements)

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“…These effects were limited when using F1M1-Fc − , suggesting that F1M1-Fc + can target NK cells to tumors and possibly also to metastases, sustaining dormancy. 7 We also found that in nude mice, NK cell depletion, by treatment with the anti-asialo GM1 antibody, impaired F1M1-Fc + therapeutic efficacy in MDA-MB-231 TNBC cell xenografts, demonstrating the key role of tumorinfiltrating NK cells in F1M1-Fc + effect. Interestingly, the limited antitumor activity of F1M1-Fc + observed in mice treated with the anti-asialo GM1 antibody was very similar to that observed with F1M1-Fc − , which depends solely on Fab-mediated effector functions.…”

Section: Discussionmentioning

confidence: 52%

“…[4][5][6] Using mouse TNBC models, it was shown that NK cells are selectively increased in the dormant milieu, and that adjuvant IL15-based immunotherapy ensures an abundant pool of NK cells to sustain dormancy, thus preventing liver metastasis formation and prolonging survival. 7 By phenotyping the NK cell infiltrates in MDA-MB-231 cell xenografts, we observed that only treatment with F1M1-Fc + led to the tumor recruitment of immature CD27 -CD11b -NK and mature stage 1 CD27 + CD11b − NK cells that were undergoing activation, as indicated by the concomitant upregulation of the Eomes transcription factor. 35 Moreover, following F1M1-Fc + treatment, the cell surface expression of CD107a, a functional marker of NK cell degranulation, and the intracellular expression of granzyme B, a marker of NK cell cytotoxic activity, were significantly increased in NK cells that infiltrated MDA-MB-231 cell xenografts.…”

Section: Discussionmentioning

confidence: 89%

“…2 3 Recent studies and clinical trials highlighted that natural killer (NK) cell-based immunotherapy can awake the innate anticancer response, particularly against tumor metastases, [4][5][6] and sustain BC dormancy. 7 Hence, different immunotherapeutic strategies are tested to improve the efficacy of antibody-induced NK cell-mediated antitumor activity. Glycoengineering and protein-engineering of the Fc region of tumor-targeting antibodies have been exploited to modulate their interaction with activating or inhibitory members of the FcγR family.…”

Section: Introductionmentioning

confidence: 99%

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A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer

Desroys du Roure,

Lajoie,

Mallavialle

et al. 2024

J Immunother Cancer

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IntroductionTriple-negative breast cancer (TNBC) prognosis is poor. Immunotherapies to enhance the antibody-induced natural killer (NK) cell antitumor activity are emerging for TNBC that is frequently immunogenic. The aspartic protease cathepsin D (cath-D), a tumor cell-associated extracellular protein with protumor activity and a poor prognosis marker in TNBC, is a prime target for antibody-based therapy to induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). This study investigated whether Fc-engineered anti-cath-D antibodies trigger ADCC, their impact on antitumor efficacy and tumor-infiltrating NK cells, and their relevance for combinatory therapy in TNBC.MethodsCath-D expression and localization in TNBC samples were evaluated by western blotting, immunofluorescence, and immunohistochemistry. The binding of human anti-cath-D F1M1 and Fc-engineered antibody variants, which enhance (F1M1-Fc+) or prevent (F1M1-Fc−) affinity for CD16a, to secreted human and murine cath-D was analyzed by ELISA, and to CD16a by surface plasmon resonance and flow cytometry. NK cell activation was investigated by flow cytometry, and ADCC by lactate dehydrogenase release. The antitumor efficacy of F1M1 Fc-variants was investigated using TNBC cell xenografts in nude mice. NK cell recruitment, activation, and cytotoxic activity were analyzed in MDA-MB-231 cell xenografts by immunophenotyping and RT-qPCR. NK cells were depleted using an anti-asialo GM1 antibody. F1M1-Fc+antitumor effect was assessed in TNBC patient-derived xenografts (PDXs) and TNBC SUM159 cell xenografts, and in combination with paclitaxel or enzalutamide.ResultsCath-D expression on the TNBC cell surface could be exploited to induce ADCC. F1M1 Fc-variants recognized human and mouse cath-D. F1M1-Fc+activated NK cells in vitro and induced ADCC against TNBC cells and cancer-associated fibroblasts more efficiently than F1M1. F1M1-Fc−was ineffective. In the MDA-MB-231 cell xenograft model, F1M1-Fc+displayed higher antitumor activity than F1M1, whereas F1M1-Fc−was less effective, reflecting the importance of Fc-dependent mechanisms in vivo. F1M1-Fc+triggered tumor-infiltrating NK cell recruitment, activation and cytotoxic activity in MDA-MB-231 cell xenografts. NK cell depletion impaired F1M1-Fc+antitumor activity, demonstrating their key role. F1M1-Fc+inhibited growth of SUM159 cell xenografts and two TNBC PDXs. In combination therapy, F1M1-Fc+improved paclitaxel and enzalutamide therapeutic efficacy without toxicity.ConclusionsF1M1-Fc+is a promising immunotherapy for TNBC that could be combined with conventional regimens, including chemotherapy or antiandrogens.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer

Desroys du Roure,

Lajoie,

Mallavialle

et al. 2024

J Immunother Cancer

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“…The activation of HSCs and the secretion of CXCL12 act on CXCR4 in NK cells and determines their quiescency. CXCL12 expression and HSC abundance are closely correlated in patients with liver metastases, mirroring the interplay between the immune response and the hepatic microenvironment [ 96 ].…”

Section: The Cells Of Innate Immunity and Their Role According To The...mentioning

confidence: 99%

The Innate Immune Microenvironment in Metastatic Breast Cancer

Tommasi

Pellegrino

Diana³

et al. 2022

JCM

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The immune system plays a fundamental role in neoplastic disease. In the era of immunotherapy, the adaptive immune response has been in the spotlight whereas the role of innate immunity in cancer development and progression is less known. The tumor microenvironment influences the terminal differentiation of innate immune cells, which can explicate their pro-tumor or anti-tumor effect. Different cells are able to recognize and eliminate no self and tumor cells: macrophages, natural killer cells, monocytes, dendritic cells, and neutrophils are, together with the elements of the complement system, the principal players of innate immunity in cancer development and evolution. Metastatic breast cancer is a heterogeneous disease from the stromal, immune, and biological point of view and requires deepened exploration to understand different patient outcomes. In this review, we summarize the evidence about the role of innate immunity in breast cancer metastatic sites and the potential targets for optimizing the innate response as a novel treatment opportunity.

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Glioblastoma cell fate is differentially regulated by the microenvironments of the tumor bulk and infiltrative margin

et al. 2023

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Author Correction: Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy

Cited by 5 publications

References 0 publications

A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer

A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer

The Innate Immune Microenvironment in Metastatic Breast Cancer

Glioblastoma cell fate is differentially regulated by the microenvironments of the tumor bulk and infiltrative margin

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