Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma

By T. Simpson, Fubin Li, Welby Montalvo-Ortiz, Manuel A. Sepulveda, K. Bergerhoff, F. Arce, C. Roddie, J. Henry, H. Yagita, J. Wolchok and 4 more. Journal of Experimental Medicine, 2013

1,396 citations recorded by the source corpus.

Anti–CTLA-4 antibody induces selective depletion of T reg cells within tumor lesions in a manner that is dependent on the presence of Fc gamma receptor-expressing macrophages within the tumor microenvironment.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/2f29a2e302641bd88202ac0606b7d660e49e15fb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Erika L. Pearce
2. W. Zou
3. J. Wolchok
4. A. Mantovani
5. Lieping Chen
6. P. Allavena
7. Michael D. Buck
8. Atsushi Tanaka

In Oncology

1. W. Zou
2. A. Mantovani
3. J. Wolchok
4. P. Allavena
5. Lieping Chen
6. Ton N. Schumacher
7. M. Gubin
8. D. Thommen

Citations in the corpus

• Systemic Immunity is Required for Effective Cancer Immunotherapy (2017, neutral): “For example, in the case of CTLA-4 blockade, administering antibody into the tumor can induce rejection (Simpson et al., 2013) and is dependent on Fcg receptors (Bulliard et al., 2013), consistent with depleting intratumoral regulatory T cells and releasing local effector cells.”
• Regulatory T Cells and Human Disease. (2020, background): “Recent studies, however, have demonstrated that ipilimumab predominantly kills CTLA-4-expressing Tregs in tumor tissues by antibody-dependent cellular cytotoxicity (ADCC), at least in mouse models (178, 181, 182).”
• Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis (2015, background): “Thus, if the CTLA-4 blockade enhances the intratumoral T-effector/T-regulator cell ratio in cancer patients, by depleting T-regulator cells [108], immunotherapy modulating CTLA-4 (such as abatacept) improves the regulatory T-cell inhibitory function in rheumatoid arthritis patients [109].”
• T Cell Dysfunction in Cancer (2018, background): “CTLA-4 blockade has also been suggested to target regulatory T cells by either functional inhibition or depletion of this subset (Duraiswamy et al., 2013; Simpson et al., 2013).”
• Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer (2013, background): “Furthermore, macrophages that are capable of engaging in Fc receptor-mediated Treg cell clearance (23) were abundant in tumors treated with AMD3100 (SI Appendix, Fig.”
• PD-L1 (B7-H1) and PD-1 Pathway Blockade for Cancer Therapy: Mechanisms, Response Biomarkers and Combinations (2016, background): “Anti–CTLA-4 antibody may deplete Tregs in the tumor (122).”
• Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade (2017, neutral): “The magnitude of this decrease was greater following CTLA-4 blockade, consistent with findings that treatment with anti-CTLA-4 leads to intratumoral Treg depletion in murine tumor models (Selby et al., 2013; Simpson et al., 2013).”