LTX-315-enabled, radiotherapy-boosted immunotherapeutic control of breast cancer by NK cells
| Autor: | Aitziber Buqué, Erik Wennerberg, Baldur Sveinbjørnsson, Jeffrey Kraynak, Lorenzo Galluzzi, Michal Hensler, Sandra Demaria, Øystein Rekdal, Xi Kathy Zhou, Jitka Fucikova, Takahiro Yamazaki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Immunology Triple Negative Breast Neoplasms cdc1s immune checkpoint inhibitors Mice Breast cancer Immune system Immunity Tumor Microenvironment medicine Animals Humans Immunology and Allergy ts/a cells RC254-282 Original Research Tumor microenvironment business.industry pd-1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens mpa/dmba-driven mammary carcinomas RC581-607 medicine.disease Oncolytic virus Killer Cells Natural Radiation therapy ctla4 Oncology Cancer cell Cancer research Immunotherapy Immunologic diseases. Allergy Breast carcinoma business Oligopeptides Research Article |
| Zdroj: | OncoImmunology, Vol 10, Iss 1 (2021) Oncoimmunology article-version (VoR) Version of Record |
| Popis: | LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and clinical evidence indicates that the anticancer properties of LTX-315 originate not only from its ability to selectively kill cancer cells, but also from its capacity to promote tumor-targeting immune responses. Here, we investigated the therapeutic activity and immunological correlates of intratumoral LTX-315 administration in three syngeneic mouse models of breast carcinoma, with a focus on the identification of possible combinatorial partners. We found that breast cancer control by LTX-315 is accompanied by a reconfiguration of the immunological tumor microenvironment that supports the activation of anticancer immunity and can be boosted by radiation therapy. Mechanistically, depletion of natural killer (NK) cells compromised the capacity of LTX-315 to limit local and systemic disease progression in a mouse model of triple-negative breast cancer, and to extend the survival of mice bearing hormone-accelerated, carcinogen-driven endogenous mammary carcinomas. Altogether, our data suggest that LTX-315 controls breast cancer progression by engaging NK cell-dependent immunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|