Microglia are unique tissue phagocytes with high self-renewing capacity

24 Combined analysis of antigen presentation and T cell recognition reveals restricted immune responses in melanoma

Introduction Studies in the past few years have suggested a key role for neo-antigens in cancer immunotherapy. Since neo-antigens are specifically expressed on the tumour, targeting them is not likely to induce tolerance or normal tissue toxicity, making them candidates for immunotherapy. Despite encouraging results in clinical trials using neo-antigens, peptide or RNA vaccines and adoptive cell transfer (ACT), only a handful of neo-antigens and their corresponding T-cells have been identified in patients. Material and methods In this study we are using a combination of a novel neo-antigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to unbiasedly identify tumour associ…

Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma.

Abstract The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interactions with their tumor-infiltrating lymphocytes (TIL). Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to discover remarkable antigenic and TIL similarities b…

Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System

SummaryDuring early embryogenesis, microglia arise from yolk sac progenitors that populate the developing central nervous system (CNS), but how the tissue-resident macrophages are maintained throughout the organism’s lifespan still remains unclear. Here, we describe a system that allows specific, conditional ablation of microglia in adult mice. We found that the microglial compartment was reconstituted within 1 week of depletion. Microglia repopulation relied on CNS-resident cells, independent from bone-marrow-derived precursors. During repopulation, microglia formed clusters of highly proliferative cells that migrated apart once steady state was achieved. Proliferating microglia expressed …