Dendritic cell-mediated cross presentation of tumor-derived peptides is biased against plasma membrane proteins.

Background: For effective tumor elimination, cytotoxic CD8 T cells must recognize tumor-derived antigens presented on class I major histocompatibility complex (MHC-I). Despite a general association between the expression of immunogenic antigens, typically neoantigens, and response to immunotherapy, the majority of patients lack strong endogenous responses to most putative neoantigens due to mechanisms that are not well understood. Cytotoxic CD8 T-cell responses are induced by dendritic cells (DCs) cross-presenting tumor-derived peptides on MHC-I.

Type I interferon activates MHC class I-dressed CD11b conventional dendritic cells to promote protective anti-tumor CD8 T cell immunity.

Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8 T cell responses in Batf3 mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors.

Tissue Site and the Cancer Immunity Cycle.

Checkpoint blockade immunotherapy (CBT) has revolutionized cancer treatment; however, the cellular and molecular factors that govern responsiveness to immunotherapy remain poorly understood. One emerging area of clinical importance is differential responsiveness to CBT across different tissue sites of tumor growth. Each tissue site in the body can contain unique tissue-resident immune cells from both the lymphoid and the myeloid compartment and differences in tissue-specific immune cell composition might predispose tumors in certain tissue sites to be more or less responsive to immunotherapy.

Dia1-dependent adhesions are required by epithelial tissues to initiate invasion.

Developing tissues change shape and tumors initiate spreading through collective cell motility. Conserved mechanisms by which tissues initiate motility into their surroundings are not known. We investigated cytoskeletal regulators during collective invasion by mouse tumor organoids and epithelial Madin-Darby canine kidney (MDCK) acini undergoing branching morphogenesis in collagen.

Acquired resistance to the second-generation androgen receptor antagonist enzalutamide in castration-resistant prostate cancer.

Enzalutamide (MDV3100) is a second generation Androgen Receptor (AR) antagonist with proven efficacy in the treatment of castration resistant prostate cancer (CRPC). The majority of treated patients, however, develop resistance and disease progression and there is a critical need to identify novel targetable pathways mediating resistance. The purpose of this study was to develop and extensively characterize a series of enzalutamide-resistant prostate cancer cell lines.

Cell-extrinsic consequences of epithelial stress: activation of protumorigenic tissue phenotypes.

Introduction: Tumors are characterized by alterations in the epithelial and stromal compartments, which both contribute to tumor promotion. However, where, when, and how the tumor stroma develops is still poorly understood. We previously demonstrated that DNA damage or telomere malfunction induces an activin A-dependent epithelial stress response that activates cell-intrinsic and cell-extrinsic consequences in mortal, nontumorigenic human mammary epithelial cells (HMECs and vHMECs).