Matches in SemOpenAlex for { <https://semopenalex.org/work/W3144956721> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W3144956721 abstract "Abstract Background: The heterogeneity of the breast tumor microenvironment (TME) may contribute to the lack of durable responses to immune checkpoint blockade (ICB), however, mouse models to test this are currently lacking. Proper choice and use of pre-clinical models are necessary for rigorous, pre-clinical studies to rapidly move laboratory findings into the clinic to treat patients. Methods: To elucidate how tumor latency and the heterogeneity of the TME contributes to ICB resistance, we performed comprehensive characterization of the TME using quantitative flow-cytometry and RNA expression analysis (NanoString) utilizing three distinct breast cancer models, all derived from the same autochthonous model. Tumor cells were obtained from the commonly used MMTV-PyMT murine breast cancer model and 1E6, 1E5 or 1E4 cells were either immediately injected into the mammary fat pad of FVB/NJ wild type mice or frozen (i.e. the tumor inoculation derived from the MMTV-PyMT tumors were never cultured). We then correlated the immunophenotyping to the efficacy observed from ICB. Results: These studies reveal that the number of cells used to generate syngeneic tumors significantly influences tumor latency, the infiltrating leukocyte population and response to ICB. The 4 models had vastly different TMEs which correlated to responses to ICB. Compared to the autochthonous model, all three syngeneic models had significantly more tumor infiltrating lymphocytes (TILs; CD3 + , CD4 + , and CD8 + ) and higher proportions of PD-L1 positive myeloid cells, whereas the MMTV-PyMT model had the highest frequency of myeloid cells out of total leukocytes. Increased TILs correlated with response to anti-PD-L1 and anti-CTLA-4 therapy; but tumor cell PD-L1expression and T-cell PD-1 expression did not. Conclusions: Here we have identified ICB-sensitive and resistant breast cancer models, generated from the same tumor cell inoculum. These models represent an opportunity to further interrogate the TME for breast cancer treatment and provide novel insights into therapeutic combinations and response to ICB. We believe this work serves as an important resource for the field to inform proper mouse model selection for pre-clinical studies." @default.
- W3144956721 created "2021-04-13" @default.
- W3144956721 creator A5001531775 @default.
- W3144956721 creator A5003864663 @default.
- W3144956721 creator A5022857112 @default.
- W3144956721 creator A5027075360 @default.
- W3144956721 creator A5029062544 @default.
- W3144956721 creator A5048186675 @default.
- W3144956721 creator A5048695888 @default.
- W3144956721 creator A5076412545 @default.
- W3144956721 date "2020-08-13" @default.
- W3144956721 modified "2023-09-27" @default.
- W3144956721 title "Use of Murine Models to Identify Tumor Immune Components that Correlate with Response to Immunotherapy in Breast Cancer" @default.
- W3144956721 doi "https://doi.org/10.21203/rs.3.rs-57679/v1" @default.
- W3144956721 hasPublicationYear "2020" @default.
- W3144956721 type Work @default.
- W3144956721 sameAs 3144956721 @default.
- W3144956721 citedByCount "0" @default.
- W3144956721 crossrefType "posted-content" @default.
- W3144956721 hasAuthorship W3144956721A5001531775 @default.
- W3144956721 hasAuthorship W3144956721A5003864663 @default.
- W3144956721 hasAuthorship W3144956721A5022857112 @default.
- W3144956721 hasAuthorship W3144956721A5027075360 @default.
- W3144956721 hasAuthorship W3144956721A5029062544 @default.
- W3144956721 hasAuthorship W3144956721A5048186675 @default.
- W3144956721 hasAuthorship W3144956721A5048695888 @default.
- W3144956721 hasAuthorship W3144956721A5076412545 @default.
- W3144956721 hasBestOaLocation W31449567211 @default.
- W3144956721 hasConcept C121608353 @default.
- W3144956721 hasConcept C126322002 @default.
- W3144956721 hasConcept C167672396 @default.
- W3144956721 hasConcept C196166836 @default.
- W3144956721 hasConcept C203014093 @default.
- W3144956721 hasConcept C2776090121 @default.
- W3144956721 hasConcept C2776107976 @default.
- W3144956721 hasConcept C2776187077 @default.
- W3144956721 hasConcept C2777701055 @default.
- W3144956721 hasConcept C2778326572 @default.
- W3144956721 hasConcept C2779282312 @default.
- W3144956721 hasConcept C2780674031 @default.
- W3144956721 hasConcept C2780851360 @default.
- W3144956721 hasConcept C2908647359 @default.
- W3144956721 hasConcept C502942594 @default.
- W3144956721 hasConcept C530470458 @default.
- W3144956721 hasConcept C553184892 @default.
- W3144956721 hasConcept C71924100 @default.
- W3144956721 hasConcept C86803240 @default.
- W3144956721 hasConcept C8891405 @default.
- W3144956721 hasConcept C99454951 @default.
- W3144956721 hasConceptScore W3144956721C121608353 @default.
- W3144956721 hasConceptScore W3144956721C126322002 @default.
- W3144956721 hasConceptScore W3144956721C167672396 @default.
- W3144956721 hasConceptScore W3144956721C196166836 @default.
- W3144956721 hasConceptScore W3144956721C203014093 @default.
- W3144956721 hasConceptScore W3144956721C2776090121 @default.
- W3144956721 hasConceptScore W3144956721C2776107976 @default.
- W3144956721 hasConceptScore W3144956721C2776187077 @default.
- W3144956721 hasConceptScore W3144956721C2777701055 @default.
- W3144956721 hasConceptScore W3144956721C2778326572 @default.
- W3144956721 hasConceptScore W3144956721C2779282312 @default.
- W3144956721 hasConceptScore W3144956721C2780674031 @default.
- W3144956721 hasConceptScore W3144956721C2780851360 @default.
- W3144956721 hasConceptScore W3144956721C2908647359 @default.
- W3144956721 hasConceptScore W3144956721C502942594 @default.
- W3144956721 hasConceptScore W3144956721C530470458 @default.
- W3144956721 hasConceptScore W3144956721C553184892 @default.
- W3144956721 hasConceptScore W3144956721C71924100 @default.
- W3144956721 hasConceptScore W3144956721C86803240 @default.
- W3144956721 hasConceptScore W3144956721C8891405 @default.
- W3144956721 hasConceptScore W3144956721C99454951 @default.
- W3144956721 hasLocation W31449567211 @default.
- W3144956721 hasLocation W31449567212 @default.
- W3144956721 hasOpenAccess W3144956721 @default.
- W3144956721 hasPrimaryLocation W31449567211 @default.
- W3144956721 hasRelatedWork W2938706471 @default.
- W3144956721 hasRelatedWork W3034810867 @default.
- W3144956721 hasRelatedWork W3096715224 @default.
- W3144956721 hasRelatedWork W3197238489 @default.
- W3144956721 hasRelatedWork W3217412908 @default.
- W3144956721 hasRelatedWork W4224222365 @default.
- W3144956721 hasRelatedWork W4281389645 @default.
- W3144956721 hasRelatedWork W4286629873 @default.
- W3144956721 hasRelatedWork W4304979265 @default.
- W3144956721 hasRelatedWork W4360983034 @default.
- W3144956721 isParatext "false" @default.
- W3144956721 isRetracted "false" @default.
- W3144956721 magId "3144956721" @default.
- W3144956721 workType "article" @default.