Dissertations and Theses (Open Access)
Author ORCID Identifier
https://orcid.org/0000-0002-8132-1804
Date of Graduation
5-2026
Document Type
Dissertation (PhD)
Program Affiliation
Immunology
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Matthew M. Gubin, PhD
Committee Member
Stephanie S. Watowich, PhD
Committee Member
James P. Allison, PhD
Committee Member
Gregory A. Lizee, PhD
Committee Member
Maria Teresa Bertilaccio, PhD
Committee Member
Mauro Di Pilato, PhD
Abstract
Type 1 conventional dendritic cells (cDC1s) are important for generating and sustaining antitumor immunity. Accordingly, the abundance of cDC1s in human tumors correlates with improved outcomes in cancer. Capitalizing on this role, we previously demonstrated that vaccination with in vitro-derived murine cDC1s elicits durable tumor control in multiple preclinical models; however, the immunological mechanisms underlying the efficacy of cDC1 vaccination remain unclear. Here, we examined whether in vitro-derived cDC1s resemble tumor-infiltrating DC populations and whether MHC-I and MHC-II antigen presentation contribute to cDC1-mediated tumor control following vaccination in melanoma.
As expected, MHC-I- or MHC-II-deficiency had minimal impact on the transcriptional state of cDC1s in homeostasis or following stimulation with the adjuvant poly dI:dC. Moreover, in vitro-derived cDC1s cultured under steady-state conditions closely resembled tumor-infiltrating cDC1s, whereas their poly dI:dC-stimulated counterparts resembled CCR7+ tumor-infiltrating DC populations, also referred to as mregDCs or LAMP3+ DCs. Analysis of tumor-infiltrating lymphocytes revealed that WT cDC1 vaccination increased accumulation of CD8+ T cells, CD4+ T cells, and IFN-γ+CD8+ T cells within tumors, as well as increased CD8+:Treg and effector CD4+:Treg ratios, whereas disruption of either MHC-I or MHC-II reduced these features. Notably, improved CD8+ and CD4+:Treg ratios reflected increased accumulation of effector T cells rather than decreased Treg abundance, indicating preferential expansion of effector populations. These changes were most pronounced within tumors over tumor-draining lymph nodes. Our data further show that both MHC-I and MHC-II contribute to tumor control upon cDC1 vaccination, and coexpression of MHC-I and MHC-II on the same cDC1 is necessary for a robust vaccine response. We also identified an important function for host cDC1s in supporting the efficacy of vaccination with in vitro-derived cDC1s, as judged by impaired tumor control in Irf8+32-/- mice, which lack endogenous cDC1s. Overall, these results indicate that effective antitumor responses depend on MHC-I and MHC-II antigen presentation by vaccine-delivered cDC1s, with additional contributions from host cDC1s.
Recommended Citation
Pineda, Josue E., "From Antigen Presentation to Tumor Control: Mechanisms of Type I Conventional Dendritic Cell-Based Cancer Vaccines" (2026). Dissertations and Theses (Open Access). 1542.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1542
Keywords
dendritic cells, vaccines, MHC class I, MHC class II, antigen presentation, cancer vaccines, immunology, immunotherapy
Included in
Biology Commons, Cancer Biology Commons, Cell Biology Commons, Immunity Commons, Immunotherapy Commons