Hirschhorn, Daniel, Budhu, Sadna, Schroder, David, Kraehenbuehl, Lukas, Flammar, Anne-Laurent, Chow, Andrew, Schulze, Isabell, Schad, Sara, Ricca, Jacob, Gasmi, Billel, De Henau, Olivier, Mangarin, Levi, Redmond, David, Cortez, Czrina, Liu, Cailian, Holland, Aliya, Gigoux, Mathieu, Arora, Asrhi, Panageas, Katherine, Rizzuto, Gabrielle, Albrengues, Jean, Egeblad, Mikala, Wolchok, Jedd, Merghoub, Taha (November 2021) T CELL IMMUNOTHERAPIES TRIGGER NEUTROPHIL ACTIVATION TO ELIMINATE TUMOR ANTIGEN ESCAPE VARIANTS. In: SITC 36th Anniversary Annual Meeting (SITC 2021).
Abstract
<jats:sec><jats:title>Background</jats:title><jats:p>Targeted immune-based therapies such as adoptive T cell transfer (ACT) are often ineffective because tumors evolve over time and under selective pressure display antigen loss variant clones. A classic example in melanoma is de-differentiation and loss of expression of antigenic proteins. Therapies that activate multiple branches of the immune system may eliminate such escape variants</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Here we show that melanoma-specific CD4+ ACT therapy in combination with OX40 co-stimulation or CTLA-4 blockade can eradicate large melanoma tumors with clonal escape variants.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Early on-target recognition of melanoma antigens by adoptively transferred tumor-specific CD4+ T cells was required. Surprisingly, however, complete tumor eradication was partially dependent on neutrophils. Supporting these findings, extensive neutrophil activation and neutrophil extracellular traps were found in mouse tumors and in biopsies of melanoma patients treated with immune checkpoint blockade.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our findings uncover a novel interplay between T cells mediating the initial tumor- and tissue-specific immune response, and neutrophils mediating tumor destruction of antigen loss variants.</jats:p></jats:sec><jats:sec><jats:title>Ethics Approval</jats:title><jats:p>All tissues were collected at MSKCC following study protocol approval by the MSKCC Institutional Review Board. All mouse procedures were performed in accordance with institutional protocol guidelines at Memorial Sloan-Kettering Cancer Center (MSKCC) under an approved protocol.</jats:p></jats:sec>
| Item Type: | Conference or Workshop Item (Paper) |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle > Neutrophil extracellular traps diseases & disorders > cancer > cancer types > melanomas organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils |
| CSHL Authors: | |
| Communities: | CSHL labs > Egeblad lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | November 2021 |
| Date Deposited: | 21 Apr 2022 14:33 |
| Last Modified: | 21 Apr 2022 14:33 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/40592 |
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