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Review
. 2024 Jul 11;16(14):2519.
doi: 10.3390/cancers16142519.

B7H4 Role in Solid Cancers: A Review of the Literature

Miriam Dawidowicz  1 , Anna Kot  2 , Sylwia Mielcarska  2 , Katarzyna Psykała  2 , Agnieszka Kula  1 , Dariusz Waniczek  1 , Elżbieta Świętochowska  2
Affiliations
Review

B7H4 Role in Solid Cancers: A Review of the Literature

Miriam Dawidowicz et al. Cancers (Basel). .

Abstract

Anti-cancer immunotherapies entirely changed the therapeutic approach to oncological patients. However, despite the undeniable success of anti-PD-1, PD-L1, and CTLA-4 antibody treatments, their effectiveness is limited either by certain types of malignancies or by the arising problem of cancer resistance. B7H4 (aliases B7x, B7H4, B7S1, VTCN1) is a member of a B7 immune checkpoint family with a distinct expression pattern from classical immune checkpoint pathways. The growing amount of research results seem to support the thesis that B7H4 might be a very potent therapeutic target. B7H4 was demonstrated to promote tumour progression in immune "cold" tumours by promoting migration, proliferation of tumour cells, and cancer stem cell persistence. B7H4 suppresses T cell effector functions, including inflammatory cytokine production, cytolytic activity, proliferation of T cells, and promoting the polarisation of naïve CD4 T cells into induced Tregs. This review aimed to summarise the available information about B7H4, focusing in particular on clinical implications, immunological mechanisms, potential strategies for malignancy treatment, and ongoing clinical trials.

Keywords: B7 family; B7H4; immune checkpoint; immunological tumour microenvironment; immunotherapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
B7H4 structure and function. Figure upper part, the effect of B7H4 interaction with its receptor (unknown). Figure lower part, the effect of B7H4 knockdown on tumour cells. APC-antigen presenting cells; Treg, regulator T cells; TAMs, tumour associated macrophages; EMT, epithelial-to-mesenchymal transition.
Figure 2
Figure 2
Cold and hot immune tumour microenvironment. The leading cellular players shaping iTME composition in the hot tumour phenotype (A) and the cold tumour phenotype (B). NK, natural killer cells; M1, macrophages of type 1; M2, macrophages of type 2; MDSC, myeloid-derived suppressor cells; Tc CD8, T cells CD8 lymphocytes; Tc CD4, T cells CD4 lymphocytes; T reg, regulator T cells; PD-L1, programmed cell death-ligand 1; B7H4, B7 homolog 4.
Figure 3
Figure 3
Basic overview of immunotherapeutic approaches targeting B7H4. Monoclonal antibodies; Adoptive cell therapy, CAR T cells; Antibody–drug conjugates; Bispecific antibodies.
See this image and copyright information in PMC

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