B7-H3 in Colorectal Adenocarcinoma: Are We Focusing on the Right Target?

B7-H3 plays a crucial role in the modulation of immune response and emerging data suggest that this transmembrane protein could promote cancer progression by coinhibitory effects on T cell responses. Limited data are available on B7-H3 expression in colorectal adenocarcinoma (CRC). This study demonstrated that most CRCs show a significant B7-H3 expression in the neoplastic-associated stroma and that this biomarker may represent a promising therapeutic target in CRC. Introduction: B7-H3 belongs to B7 protein family which comprises molecules located on the cell surface, that play a crucial role in the modulation of immune response. Emerging data suggest that B7-H3 could promote cancer progression by coinhibitory effects on T cell responses, allowing cancer cells to avoid immune response, favoring invasion, metastatic spread, and drug resistance. Nevertheless, conflicting data regarding B7-H3 tumor expression, clinical correlation, and therapy response are reported. This is mainly due to (1) different investigated populations, (2) methods employed to assess its expression, and (3) the lack of standardized guidelines for B7-H3 expression scoring. Materials and Methods: We investigated, on the whole sections, the immunohistochemical expression of B7-H3 (clone D9M2L) in a cohort of 87 patients affected by localized colorectal cancer (CRC, stage I-III), retrospectively selected to be representative of the different CRC histotypes, according to WHO, 2019 edition. Results: Positive B7-H3 staining was documented in 68/89 cases (76.5%). All 68 cases showed immunostaining in neoplastic stroma, whereas non-neoplastic tissue was unstained in all 55 cases with normal mucosa and in 5 cases of dysplasia (100%). The highest frequency of B7-H3 positivity was observed in the CRC, NOS histotype (86%). The positivity rate in NOS histotype is even higher (90.5%), when only low-grade cases are considered, whereas lower rates (73.3%) were reported in the high-grade subgroup. Conclusion: The presented data provide further evidence on the role of B7-H3 in CRC with particular reference to the tumor microenvironment and histotype, with a possible implication for the CRC therapy. Further studies are required to both confirm these data and elucidate the role of B7-H3 as a potential target to unleash the response to immunotherapy in CRC.