SUSD2-IL-2 receptor interaction hinders antitumoral CD8+ T-cell activity: Implications for cancer immunotherapy

Article Immunology

Immunoprofiling Reveals Novel Mast Cell Receptors and the Continuous Nature of Human Lung Mast Cell Heterogeneity

Elin Ronnberg et al.

Summary: A comprehensive analysis of cell-surface markers on human lung mast cells revealed the expression of more than 100 markers, including 23 previously undescribed ones. However, no distinct mast cell subpopulations were identified, indicating the continuous nature of human lung mast cell heterogeneity.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

CD8+ T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy

Abhinav Kaushik et al.

Summary: This study analyzed immune cells from participants in a peanut oral immunotherapy (OIT) trial and found that the differentiation status of CD8(+) T cells at baseline may predict the likelihood of achieving sustained unresponsiveness (SU). The study also found that lower frequencies of naïve CD8(+) T cells and terminally differentiated CD57(+)CD8(+) T cell subsets at baseline were associated with SU, while higher frequencies of IL-4(+) and IFN gamma(+) CD4(+) T cells post-OIT were correlated with a lower likelihood of SU.

NATURE COMMUNICATIONS (2022)

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Article Immunology

SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling

Bao Zhao et al.

Summary: The study suggests that SUSD2 acts as a negative regulator of CD8(+) T cells in the tumor microenvironment by interfering with the IL-2 receptor alpha and suppressing the binding of IL-2 to the receptor. Dysfunctional CD8(+) T cells, which fail to produce effective antitumor molecules, contribute to immunosuppression in tumors. The researchers found that altering SUSD2 expression enhances the production of antitumor molecules in CD8(+) T cells, leading to reduced tumor growth in mouse models, indicating the potential of SUSD2 as a target for cancer immunotherapy.

NATURE IMMUNOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Beyond immune checkpoint blockade: emerging immunological strategies

Shawn P. Kubli et al.

Summary: The review discusses the history of immunotherapy and checkpoint blockade, emphasizing key clinical failures. It highlights critical aspects of immune processes within the tumor microenvironment, which may guide the development of new therapeutic strategies in immuno-oncology. Future successful therapeutics are likely to focus on rescuing T cell homing and dysfunction in the tumor microenvironment, as well as reappropriating mononuclear phagocyte function for inflammatory remodeling of the TME. New drugs will need to consider the complex cell networks within tumors and across different cancer types.

NATURE REVIEWS DRUG DISCOVERY (2021)

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Article Biochemistry & Molecular Biology