Ionic immune suppression within the tumour microenvironment limits T cell effector function
T-cell activation depended on a critical range of internal potassium concentration; above this limit, T cells were suppressed. Potassium released from dying tumor cells promotes a protumor microenvironment, and normalizing intracellular potassium enhanced tumor clearance.
AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies
Patients with AIRE deficiency lack central T cell tolerance. They produce high-affinity autoantibodies due to an ineffective T cell–dependent B-cell checkpoint that thwarts self-reactivity. However, such autoantibodies can be therapeutically valuable to combat autoimmune or inflammatory conditions.
Normalizing retinoic acid depletion driven by microbiota or other inflammatory conditions attenuates colon tumorigenesis
Image: Penny et al. Supplementary Fig. S1
Altered retinoic acid metabolism was found to contribute to colonic inflammation and tumorigenesis. Restoring local colonic retinoic acid by preventing its catabolism in two different models of inflammation-driven colon cancer promoted protective immunity and reduced tumor growth.
A distinct gene module for dysfunction uncoupled from activation in tumor-infiltrating T cells
Intratumoral CD8+ T cells can become exhausted. Untangling the expressed genetic profiles of single CD8+ T cells revealed distinct signatures for activation and dysfunction. Metallothionein-regulated GATA-3 was found to be key to the dysfunction of intratumoral CD8+ T cells.
Lack of immunoediting in murine pancreatic cancer reversed with neoantigen
Image: Fig. 1C from Evans et al.
Tumors with multiple neoepitopes respond to T-cell pressure by adapting and escaping. Although such immunoediting was not observed in a pancreatic tumor with few neoantigens, this reflected immune quiescence from poor tumor antigenicity. Introducing a neoantigen not only initiated a T-cell response but also restored the immunoediting phenotype.
Cutting edge: IgE plays an active role in tumor immunosurveillance in mice
Image: 1F6A IgEFc bound to FcϵR1 http://www.rcsb.org/pdb/ngl/ngl.do?pdbid=1f6a
Exogenous IgE can be an adjuvant, but the role of endogenous tumor-specific IgE is less clear. Mice without IgE were more susceptible to tumors. IgE protection was mediated through the FcϵRI Fc receptor and dependent upon CD8+ T cells.
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