A Metabolic Gene Survey Pinpoints Fucosylation as a Key Pathway Underlying the Suppressive Function of Regulatory T Cells in Cancer.

Forkhead box P3 (Foxp3)-expressing regulatory T cells (Treg) are the guardians of controlled immune reactions and prevent the development of autoimmune diseases. However, in the tumor context, their increased number suppresses antitumor immune responses, indicating the importance of understanding the mechanisms behind their function and stability. Metabolic reprogramming can affect Foxp3 regulation and, therefore, Treg suppressive function and fitness.

Metabolic traits ruling the specificity of the immune response in different cancer types.

Cancer immunotherapy aims to augment the response of the patient's own immune system against cancer cells. Despite effective for some patients and some cancer types, the therapeutic efficacy of this treatment is limited by the composition of the tumor microenvironment (TME), which is not well-suited for the fitness of anti-tumoral immune cells. However, the TME differs between cancer types and tissues, thus complicating the possibility of the development of therapies that would be effective in a large range of patients.

Impact of Immunometabolism on Cancer Metastasis: A Focus on T Cells and Macrophages.

Despite improved treatment options, cancer remains the leading cause of morbidity and mortality worldwide, with 90% of this mortality correlated to the development of metastasis. Since metastasis has such an impact on treatment success, disease outcome, and global health, it is important to understand the different steps and factors playing key roles in this process, how these factors relate to immune cell function and how we can target metabolic processes at different steps of metastasis in order to improve cancer treatment and patient prognosis. Recent insights in immunometabolism direct to promising therapeutic targets for cancer treatment, however, the specific contribution of metabolism on antitumor immunity in different metastatic niches warrant further investigation.

Establishment of a Novel Humanized Mouse Model To Investigate Activation and Depletion of Patient-Derived HIV Latent Reservoirs.

Curing HIV infection has been thwarted by the persistent reservoir of latently infected CD4 T cells, which reinitiate systemic infection after antiretroviral therapy (ART) interruption. To evaluate reservoir depletion strategies, we developed a novel preclinical model consisting of immunodeficient mice intrasplenically injected with peripheral blood mononuclear cells (PBMC) from long-term ART-suppressed HIV-infected donors. In the absence of ART, these mice developed rebound viremia which, 2 weeks after PBMC injection, was 1,000-fold higher (mean = 9,229,281 HIV copies/ml) in mice injected intrasplenically than in mice injected intraperitoneally (mean = 6,838 HIV copies/ml) or intravenously (mean = 591 HIV copies/ml).

T-Cell Receptor (TCR) Clonotype-Specific Differences in Inhibitory Activity of HIV-1 Cytotoxic T-Cell Clones Is Not Mediated by TCR Alone.

Functional analysis of T-cell responses in HIV-infected individuals has indicated that virus-specific CD8 T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progressors. To define the role of individual T-cell receptor (TCR) clonotypes in differential antiviral CD8 T-cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8 T-cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK). Effective and ineffective CD8 T-cell clones segregated based on responses to HIV-1-infected and peptide-loaded target cells.