B7H3 Role in Reshaping Immunosuppressive Landscape in MSI and MSS Colorectal Cancer Tumours

Abstract

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention

“…Investigations on B7-H3 are generating considerable interest in cancer research, as it is a promising diagnostic and prognostic marker and a viable target for anticancer treatment [ 19 – 21 ]. Indeed, various clinical studies have well-established the association between B7-H3 and poor prognosis [ 10 ]. The development of immunotherapy targeting B7-H3 is rapidly evolving, with many ongoing clinical trials investigating the safety and efficacy of these therapeutic approaches in cancer patients.…”

“…Clinically, a high expression of B7-H3 and the TAM density in CRC tissue were associated with reduced overall survival of patients [ 65 ]. Studies examining the immune cells infiltrating the TME revealed that the M2 phenotype was predominantly present in the TME and indicated the presence of pro-tumor growth factors and cytokines released by M2 macrophage [ 10 , 65 ]. The JAK2-STAT3 pathway could probably mediate the polarization of macrophages [ 66 ].…”

“…However, putative receptors for B7-H3 have been identified on activated T-lymphocytes and TAMs [ 65 ]. A study by Mielcarska et al provides an exemplary observation of B7-H3 expression in the context of the immune landscape in CRC [ 10 ] investigating the CRC tissue’s tumor status, TIL, and cytokine composition [ 10 ]. The immune infiltration cell analysis showed a clear shift in the density of immune cells in the tumor correlated with B7-H3 expression [ 10 ].…”

“…A study by Mielcarska et al provides an exemplary observation of B7-H3 expression in the context of the immune landscape in CRC [ 10 ] investigating the CRC tissue’s tumor status, TIL, and cytokine composition [ 10 ]. The immune infiltration cell analysis showed a clear shift in the density of immune cells in the tumor correlated with B7-H3 expression [ 10 ]. Tumors with elevated B7-H3 expression showed reduced levels of CD4 + quiescent memory T-lymphocytes and CD4 + activated memory T-lymphocytes [ 10 ].…”

“…The immune infiltration cell analysis showed a clear shift in the density of immune cells in the tumor correlated with B7-H3 expression [ 10 ]. Tumors with elevated B7-H3 expression showed reduced levels of CD4 + quiescent memory T-lymphocytes and CD4 + activated memory T-lymphocytes [ 10 ].

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