Tocilizumab and immune signatures for targeted management of cytokine release syndrome in immune checkpoint therapy.

Background: This study aimed to identify specific biomarkers in oncology patients experiencing immune-related cytokine release syndrome (irCRS)-like symptoms during immune checkpoint inhibitor (ICI) therapy, including severe cases like hemophagocytic lymphohistiocytosis (irHLH), and to distinguish these from sepsis. A secondary objective was to retrospectively analyze the efficacy of tocilizumab (TCZ) in treating corticosteroid (CS)-refractory high-grade irCRS.

Patients And Methods: A cohort of 35 patients presenting with irCRS-like symptoms was studied, including 9 with irHLH-like manifestations and 8 with sepsis.

Primary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma.

The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69).

A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.

Therapeutic monoclonal antibodies (mAb) targeting the immune checkpoint inhibitor programmed cell death protein 1 (PD-1) have achieved considerable clinical success in anti-cancer therapy through relieving T cell exhaustion. Blockade of PD-1 interaction with its ligands PD-L1 and PD-L2 is an important determinant in promoting the functional recovery of exhausted T cells. Here, we show that anti-PD-1 mAbs act through an alternative mechanism leading to the downregulation of PD-1 surface expression on memory CD4 and CD8 T cells.

CXCL12 and CXCL13 Cytokine Serum Levels Are Associated with the Magnitude and the Quality of SARS-CoV-2 Humoral Responses.

A better understanding of the immunological markers associated with long-lasting immune responses to SARS-CoV-2 infection is of paramount importance. In the present study, we characterized SARS-CoV-2-specific humoral responses in hospitalized (ICU and non-ICU) and non-hospitalized individuals at six months post-onset of symptoms (POS) (N = 95). We showed that the proportion of individuals with detectable anti-SARS-CoV-2 IgG or neutralizing (NAb) responses and the titers of antibodies were significantly reduced in non-hospitalized individuals, compared to ICU- or non-ICU-hospitalized individuals at 6 months POS.