Medicine and Health Sciences Commons^™

Perilymphatic Irx-2 Cytokine Therapy To Enhance Tumor Infiltrating Lymphocytes And Pd-L1 Expression Preceding Curative-Intent Therapy In Early Stage Breast Cancer, Joanna Pucilowska, Venkatesh Rajamanickam, Katherine Sanchez, Valerie Conrad, Alison Conlin, Shagheyegh Aliabadi-Wahle, Shu-Ching Chang, Gary Grunkemeier, Nikki Moxon, Staci Mellinger, Maritza Martel, James Egan, Monil Shah, David B Page

Books, Presentations, Posters, Etc.

Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells, facilitates …

Tumor Infiltrating Lymphocyte Recruitment After Peri-Lymphatic Irx-2 Cytokine Immunotherapy In Resectable Breast Cancer And Head And Neck Carcinoma, Joanna Pucilowska, Venkatesh Rajamanickam, Nikki Moxon, Monil Shah, Maritza Martel, Alison Conlin, James E. Egan, David B. Page

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: The IRX-2 biologic is a subcutaneous injectable immunotherapy composed of IL-2 and other cytokines derived from stimulated lymphocytes. Preclinically, IRX-2 activates T cells, natural killer cells, macrophages, and dendritic cells, and facilitates maturation of antigen-presenting cells.Tumor-infiltrating lymphocytes (TILs) are associated with improved outcomes in many cancers including early stage breast cancer (ESBC) and head and neck squamous cell carcinoma (HNSCC). We report data on TIL recruitment associated with pre-operative IRX-2 in a phase Ib ESBC trial, as well as phase Ib and IIa HNSCC trials.

Methods: The pre-operative IRX-2 regimen was evaluated in both ESBC and HNSCC trials for …

Loss Of Inter-Cellular Cooperation By Complete Epithelial-Mesenchymal Transition Supports Favorable Outcomes In Basal Breast Cancer Patients., Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie Macintosh, Aymeric Fouquier D'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang

Articles, Abstracts, and Reports

According to the sequential metastasis model, aggressive mesenchymal (M) metastasis-initiating cells (MICs) are generated by an epithelial-mesenchymal transition (EMT) which eventually is reversed by a mesenchymal-epithelial transition (MET) and outgrowth of life-threatening epithelial (E) macrometastases. Paradoxically, in breast cancer M signatures are linked with more favorable outcomes than E signatures, and M cells are often dispensable for metastasis in mouse models. Here we present evidence at the cellular and patient level for the cooperation metastasis model, according to which E cells are MICs, while M cells merely support E cell persistence through cooperation. We tracked the fates of co-cultured E …

Tumor Mutational Burden Is A Determinant Of Immune-Mediated Survival In Breast Cancer., Alexandra Thomas, Eric D Routh, Ashok Pullikuth, Guangxu Jin, Jing Su, Jeff W Chou, Katherine A Hoadley, Cristin Print, Nick Knowlton, Michael A Black, Sandra Demaria, Ena Wang, Davide Bedognetti, Wendell D Jones, Gaurav A Mehta, Michael L Gatza, Charles M Perou, David B Page, Pierre Triozzi, Lance D Miller

Articles, Abstracts, and Reports

Mounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). …

Mir-29c Plays A Suppressive Role In Breast Cancer By Targeting The Timp3/Stat1/Foxo1 Pathway., Wan Li, Jie Yi, Xiangjin Zheng, Shiwei Liu, Weiqi Fu, Liwen Ren, Li Li, Dave S B Hoon, Jinhua Wang, Guanhua Du

Articles, Abstracts, and Reports

Background: miR-29c has been associated with the progression of many cancers. However, the function and mechanism of miR-29c have not been well investigated in breast cancers.

Methods: Real-time quantitative PCR was used to assess expression of miR-29c and DNMT3B mRNA. Western blot and immunochemistry were used to examine the expression of DNA methyltransferase 3B (DNMT3B) protein in breast cancer cells and tissues. The functional roles of miR-29c in breast cancer cells such as proliferation, migration, invasion, colony formation, and 3D growth were evaluated using MTT, transwell chambers, soft agar, and 3D Matrigel culture, respectively. In addition, the luciferase reporter assay …