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B7-H4 post-translational modifications

ABSTRACT: B7-H4 functions as an immune checkpoint in the tumor microenvironment (TME). However, the post-translational modification (PTM) of B7-H4 and its translational potential in cancer remains incompletely understood. We found that ZDHHC3, a zinc finger DHHC-type palmitoyltransferase, palmitoylates B7-H4 at Cys130 in breast cancer cells, preventing its lysosomal degradation and sustaining B7-H4-mediated immunosuppression. Knockdown of ZDHHC3 in tumors resulted in robust anti-tumor immunity and reduced tumor progression in murine models. Moreover, abemaciclib, a CDK4/6 inhibitor, primed lysosome activation and promoted lysosomal degradation of B7-H4 independently of the tumor cell cycle. Treatment with abemaciclib resulted in T cell activation and mitigated B7-H4-mediated immune suppression via inducing B7-H4 degradation in preclinical tumor models. Thus, B7-H4 palmitoylation is an undocumented PTM controlling B7-H4 protein stability and abemaciclib may be repurposed to enhance B7-H4 degradation, thereby treating patients with B7-H4+ tumors.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Weiping Zou

LAB HEAD: Weiping Zou

PROVIDER: PXD054393 | Pride | 2025-02-14

REPOSITORIES: pride

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			Action	DRS
	PRF_F_2020_W_ZOU_406_49736.msf	Msf
	PRF_F_2020_W_ZOU_406_49736.raw	Raw
	PRF_F_2020_W_ZOU_406_49737.msf	Msf
	PRF_F_2020_W_ZOU_406_49737.raw	Raw
	PRF_F_2020_W_ZOU_406_49738.msf	Msf

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