New insights into the control of T-cell activation and proliferation have led to the identification of checkpoint proteins that either up- or downmodulate T-cell reactivity. Monoclonal antibody immunotherapies that are reactive with cytotoxic T lymphocyte antigen 4 or programmed death receptor 1 have shown promising therapeutic outcomes in mice and humans with established cancer, highlighting t...

Lymphotoxin-alpha (LTalpha) was originally linked to delayed-type hypersensitivity and its production was later attributed to Th1, but not Th2 cells. Studies employing knockout mice demonstrated that LT signaling is essential for the development and functional compartmentalization of lymphoid tissues. Here, using gene expression profiling, we identified a novel gene termed SMUCKLER (spleen, muc...

Cancer-induced immunosuppression significantly impacts tumors, rendering them the ability to acquire aggressive and treatment-resistant phenotypes. The recent clinical success of drugs targeting the immunosuppressive machinery of tumors highlights the importance of identifying novel drugs that effectively augment antitumor immunity and elicit clinical remission in advanced tumors. T cell immuno...

Oncolytic viruses (OVs) remodel the tumor microenvironment by switching a “cold” into “hot” with high CD8+ T-cell infiltration. activity plays an essential role in antitumor efficacy of OVs. However, T cells is impaired programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) interaction. To date, it remains unclear why OVs alone have significant even when PD-L1 expression persist...

Successfully identifying and targeting immune checkpoints on latently HIV-1-infected CD4 T cells could be a key component in HIV-1 eradication therapies [1,2]. Immune checkpoints are negative regulators of: (i) T cell activation; (ii) T cell proliferation; and (iii) effector functions including cytokine production [3]. Thus, inhibiting immune checkpoints could influence the resting status of la...

T cell immunoglobulin and mucin domain 3 (Tim3) is a negative regulatory molecule that inhibits effector T(H)1-type responses. Such inhibitory signals prevent unintended tissue inflammation, but can be detrimental if they lead to premature T cell exhaustion. Although the role of Tim3 in autoimmunity has been extensively studied, whether Tim3 regulates antimicrobial immunity has not been explore...