TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy.

Abstract:

:Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases-TYRO3, AXL, and MERTK-as an emerging class of innate immune checkpoints that participate in key steps of anti-tumoral immunity. Namely, TAM-mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T-cell checkpoint blockade.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Akalu YT,Rothlin CV,Ghosh S

doi

10.1111/imr.12522

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

165-177

issue

1

eissn

0105-2896

issn

1600-065X

journal_volume

276

pub_type

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