Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors

Simon, Sonja C. S.; Hu, Xiaoying; Panten, Jasper; Grees, Mareike; Renders, Simon; Thomas, Daniel C.; Weber, Rebekka; Schulze, Torsten J.; Utikal, Jochen; Umansky, Viktor

doi:10.1080/2162402x.2020.1727116

Cited by 65 publications

(107 citation statements)

References 56 publications

(68 reference statements)

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“…The increase in tumor-infiltrating eosinophils in mice exposed to CTX/anti-PDL1/2 correlates with intratumoral expression of IL-33 which can both recruit and activate these cells [46]. Importantly, eosinophils are emerging as relevant immune biomarkers for response to ICIs in cancer patients, correlating with better clinical outcome [47]. In conclusion, the composition of the tumor-associated myeloid compartment plays a key role in tumor response to anti-PDL blockade.…”

Section: Discussionmentioning

confidence: 96%

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Rossi

Lucarini

Macchia

et al. 2020

Cells

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Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment providing unprecedented clinical benefits. However, many patients do not respond to ICIs as monotherapy or develop resistance. Combining ICI-based immunotherapy with chemotherapy is a promising strategy to increase response rates, but few rationale-driven chemo-immunotherapy combinations have reached the clinical arena thus far. In the present study, we show that combined anti-PDL1 and anti-PDL2 antibodies optimally synergize with cyclophosphamide but not with cisplatin, and that the magnitude and duration of the therapeutic response is dependent on the immunogenic potential of the drug and of the tumor itself. Hallmarks of successful therapeutic outcomes were the enhanced infiltration by myeloid (mainly cross-presenting dendritic cells, eosinophils, and monocytic myeloid cells) and T lymphocytes into the tumor tissue and the expansion of circulating memory pools. Overall, our results suggest that immunomodulating chemotherapy can be exploited to increase the efficacy of PD1/PDL axis inhibitors in vivo, and that the magnitude of the synergic therapeutic response is affected by tumor-intrinsic immunogenicity.

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Section: Discussionmentioning

confidence: 96%

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Rossi

Lucarini

Macchia

et al. 2020

Cells

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“…Although this study does not directly address whether IL-33 is relevant for up-regulation of these immune checkpoint molecules, it suggests that local IL-33 and eosinophils recruitment in the TME may promote immunotherapy efficacy. This hypothesis is supported by an increasing number of reports that show a positive correlation between eosinophilia and clinical response to anti-PD-1 and anti-CTLA-4 in cancer patients (47,96,97).…”

Section: Modulation Of Immune Checkpoints By Il-33mentioning

confidence: 61%

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

et al. 2020

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Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to its specific receptor ST2 expressed by most immune cell populations, modulating a variety of responses. In cancer immunity, IL-33 can display both pro-tumoral and anti-tumoral functions, depending on the specific microenvironment. Recent findings indicate that IL-33 can effectively stimulate immune effector cells (NK and CD8+ T cells), eosinophils, basophils and type 2 innate lymphoid cells (ILC2) promoting direct and indirect anti-tumoral activities. In this review, we summarize the most recent advances on anti-tumor immune mechanisms operated by IL-33, including the modulation of immune checkpoint molecules, with the aim to understand its potential as a therapeutic target in cancer.

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“…An accumulation of eosinophils has been observed in the tumor tissue and peripheral blood of cancer patients [ 127 ]. Moreover, this was reported to be associated with a beneficial OS and progression-free survival (PFS) in melanoma patients [ 128 , 129 ].…”

Section: Ev In Crosstalk Between Tumor Cells and Granulocytesmentioning

confidence: 99%

Myeloid Cell Modulation by Tumor-Derived Extracellular Vesicles

Arkhypov

Lasser

Petrova

et al. 2020

IJMS

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Extracellular vesicles (EV) can carry proteins, RNA and DNA, thus serving as communication tools between cells. Tumor cells secrete EV, which can be taken up by surrounding cells in the tumor microenvironment as well as by cells in distant organs. Tumor-derived EV (TEV) contain factors induced by tumor-associated hypoxia such as heat shock proteins or a variety of microRNA (miRNA). The interaction of TEV with tumor and host cells can promote cancer angiogenesis, invasion and metastasis. Myeloid cells are widely presented in tissues, comprise the majority of immune cells and play an essential role in immune reactions and tissue remodeling. However, in cancer, the differentiation of myeloid cells and their functions are impaired, resulting in tumor promotion. Such alterations are due to chronic inflammatory conditions associated with cancer and are mediated by the tumor secretome, including TEV. A high capacity of myeloid cells to clear EV from circulation put them in the central position in EV-mediated formation of pre-metastatic niches. The exposure of myeloid cells to TEV could trigger numerous signaling pathways. Progenitors of myeloid cells alter their differentiation upon the contact with TEV, resulting in the generation of myeloid-derived suppressor cells (MDSC), inhibiting anti-tumor function of T and natural killer (NK) cells and promoting thereby tumor progression. Furthermore, TEV can augment MDSC immunosuppressive capacity. Different subsets of mature myeloid cells such as monocytes, macrophages, dendritic cells (DC) and granulocytes take up TEV and acquire a protumorigenic phenotype. However, the delivery of tumor antigens to DC by TEV was shown to enhance their immunostimulatory capacity. The present review will discuss a diverse and complex EV-mediated crosstalk between tumor and myeloid cells in the context of the tumor type, TEV-associated cargo molecules and type of recipient cells.

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Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors

Cited by 65 publications

References 56 publications

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

Myeloid Cell Modulation by Tumor-Derived Extracellular Vesicles

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