دورية أكاديمية
أعرض في EDS

Human Tumor-Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis.

التفاصيل البيبلوغرافية
العنوان: Human Tumor-Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis.
المؤلفون: Singhal S; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Rao AS; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Stadanlick J; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Bruns K; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Sullivan NT; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Bermudez A; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Honig-Frand A; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Krouse R; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Arambepola S; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Guo E; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Moon EK; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Georgiou G; Department of Chemical Engineering, University of Texas at Austin, Austin, Texas., Valerius T; Department of Medicine II, Christian Albrechts University and University Hospital Schleswig-Holstein, Kiel, Germany., Albelda SM; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Eruslanov EB; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
المصدر: Cancer research [Cancer Res] 2024 Apr 01; Vol. 84 (7), pp. 1029-1047.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, Md. : American Association for Cancer Research
Original Publication: Chicago [etc.]
مواضيع طبية MeSH: Neutrophils*/metabolism , Neoplasms*/pathology, Humans ; Tumor-Associated Macrophages/metabolism ; Trogocytosis ; Antibody-Dependent Cell Cytotoxicity ; Phagocytosis ; Receptors, Fc ; Antigens, Neoplasm
مستخلص: The clinical benefits of tumor-targeting antibodies (tAb) are modest in solid human tumors. The efficacy of many tAbs is dependent on Fc receptor (FcR)-expressing leukocytes that bind Fc fragments of tAb. Tumor-associated macrophages (TAM) and neutrophils (TAN) represent the majority of FcR+ effectors in solid tumors. A better understanding of the mechanisms by which TAMs and TANs regulate tAb response could help improve the efficacy of cancer treatments. Here, we found that myeloid effectors interacting with tAb-opsonized lung cancer cells used antibody-dependent trogocytosis (ADT) but not antibody-dependent phagocytosis. During this process, myeloid cells "nibbled off" tumor cell fragments containing tAb/targeted antigen (tAg) complexes. ADT was only tumoricidal when the tumor cells expressed high levels of tAg and the effectors were present at high effector-to-tumor ratios. If either of these conditions were not met, which is typical for solid tumors, ADT was sublethal. Sublethal ADT, mainly mediated by CD32hiCD64hi TAM, led to two outcomes: (i) removal of surface tAg/tAb complexes from the tumor that facilitated tumor cell escape from the tumoricidal effects of tAb; and (ii) acquisition of bystander tAgs by TAM with subsequent cross-presentation and stimulation of tumor-specific T-cell responses. CD89hiCD32loCD64lo peripheral blood neutrophils (PBN) and TAN stimulated tumor cell growth in the presence of the IgG1 anti-EGFR Ab cetuximab; however, IgA anti-EGFR Abs triggered the tumoricidal activity of PBN and negated the stimulatory effect of TAN. Overall, this study provides insights into the mechanisms by which myeloid effectors mediate tumor cell killing or resistance during tAb therapy.
Significance: The elucidation of the conditions and mechanisms by which human FcR+ myeloid effectors mediate cancer cell resistance and killing during antibody treatment could help develop improved strategies for treating solid tumors.
(©2024 The Authors; Published by the American Association for Cancer Research.)
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معلومات مُعتمدة: R01 CA187392 United States CA NCI NIH HHS; T32 CA009140 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Receptors, Fc)
0 (Antigens, Neoplasm)
تواريخ الأحداث: Date Created: 20240125 Date Completed: 20240403 Latest Revision: 20240404
رمز التحديث: 20240404
مُعرف محوري في PubMed: PMC10982649
DOI: 10.1158/0008-5472.CAN-23-2135
PMID: 38270915
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-7445
DOI:10.1158/0008-5472.CAN-23-2135