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B7-H3 in Colorectal Adenocarcinoma: Are We Focusing on the Right Target?
Paola Parente1, Davide Ciardiello2, Valentina Angerilli3
1Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
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.
Insights
B7-H3 is frequently expressed in colorectal cancer (CRC) stroma, particularly in the NOS histotype. This finding suggests B7-H3 may be a therapeutic target for enhancing immunotherapy response in CRC patients.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- B7-H3 is a cell surface protein involved in immune response modulation.
- Emerging evidence suggests B7-H3 promotes cancer progression by suppressing T cell responses, aiding immune evasion, invasion, metastasis, and drug resistance.
- Conflicting data on B7-H3 expression and its clinical correlation necessitate further investigation due to varied study populations, methods, and scoring guidelines.
Purpose of the Study:
- To investigate the immunohistochemical expression of B7-H3 in localized colorectal cancer (CRC).
- To correlate B7-H3 expression with CRC histotype.
- To explore the potential role of B7-H3 in the CRC tumor microenvironment and its implications for therapy.
Main Methods:
- Immunohistochemical analysis of B7-H3 expression using clone D9M2L on whole sections.
- Study cohort comprised 87 patients with localized CRC (Stage I-III).
- Patients were retrospectively selected to represent diverse CRC histotypes per WHO 2019 classification.
Main Results:
- B7-H3 positive staining was observed in 76.5% (68/89) of CRC cases.
- Immunostaining was consistently found in the neoplastic stroma, while normal mucosa and dysplasia showed no staining (100%).
- The CRC, NOS histotype exhibited the highest frequency of B7-H3 positivity (86%), with higher rates in low-grade (90.5%) compared to high-grade (73.3%) subgroups.
Conclusions:
- The study provides evidence for B7-H3's role in CRC, particularly within the tumor microenvironment and its association with histotype.
- Findings suggest B7-H3 may have implications for CRC therapy, potentially as a target for immunotherapy.
- Further research is needed to confirm these results and fully elucidate B7-H3's potential as a therapeutic target in CRC.
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