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PD-L1 and IDO expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for
Zachary Chinn1, Mark H Stoler1, Anne M Mills1
1Department of Pathology, University of Virginia, Charlottesville, VA, USA.
Aims:
The immunoregulatory enzyme indoleamine dioxygenase 2,3 (IDO) has been implicated in cervical and vulvar squamous carcinomas (SCC) and may represent a mechanism of resistance to anti-PD-1/anti-PD-L1 therapy. However, the relationship between IDO and PD-L1 has not been well-investigated.
Methods And Results:
Sixty-five cases of cervical and vulvar intraepithelial neoplasia and SCC were assessed for IDO and PD-L1 expression. Overall, tumoral PD-L1 expression was seen in 72% of SCC, while 50% expressed IDO; co-expression was seen in 42%. Using the combined positive score (CPS) threshold of 1 to account for both tumoral and immune staining, 83% of SCC expressed PD-L1, 61% expressed IDO and 53% showed co-expression. Cervical SCCs were significantly more likely than human papillomavirus (HPV)-related vulvar SCCs to express tumoral IDO (75% versus 13%, P < 0.001) and demonstrate an IDO CPS ≥ 1 (88% versus 25%, P < 0.001); no significant differences were seen for PD-L1. Additionally, there were no significant differences in IDO and PD-L1 expression in dVIN-associated versus HPV-associated vulvar SCC. In contrast to SCC, the majority of intraepithelial lesions were entirely negative for tumoral PD-L1 and IDO and had a CPS score of <1.
Conclusions:
In summary, IDO and PD-L1 co-expression is common in cervical SCCs and, to a lesser extent, vulvar SCCs. These data suggest a role for combination immunotherapy in a subset of cervical SCCs as well as select vulvar SCCs. Expression for both markers is less common in intraepithelial lesions, providing no strong support for this form of immunotherapy in the absence of invasion.
Insights
Indoleamine dioxygenase 2,3 (IDO) and PD-L1 are frequently co-expressed in cervical squamous cell carcinomas (SCC), suggesting potential for combination immunotherapy. This co-expression is less common in vulvar SCC and rare in pre-invasive lesions.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Indoleamine dioxygenase 2,3 (IDO) is an immunoregulatory enzyme implicated in cervical and vulvar squamous cell carcinomas (SCC).
- IDO may contribute to resistance against anti-PD-1/anti-PD-L1 therapies.
- The relationship between IDO and PD-L1 expression in these cancers is not well-understood.
Purpose of the Study:
- To investigate the co-expression of IDO and PD-L1 in cervical and vulvar SCC.
- To assess the potential for combination immunotherapy based on IDO and PD-L1 expression.
Main Methods:
- Assessed IDO and PD-L1 expression in 65 cases of cervical and vulvar intraepithelial neoplasia and SCC.
- Utilized the combined positive score (CPS) threshold of 1 for tumoral and immune staining.
- Compared expression patterns between cervical SCC and human papillomavirus (HPV)-related vulvar SCC.
Main Results:
- Tumoral PD-L1 was expressed in 72% of SCC, and IDO in 50%; co-expression was observed in 42%.
- Using CPS ≥ 1, 83% of SCC expressed PD-L1, 61% expressed IDO, and 53% showed co-expression.
- Cervical SCC showed significantly higher tumoral IDO and IDO CPS ≥ 1 compared to HPV-related vulvar SCC (P < 0.001).
Conclusions:
- IDO and PD-L1 co-expression is common in cervical SCC and present in a subset of vulvar SCC.
- These findings support exploring combination immunotherapy for select cervical and vulvar SCC patients.
- Limited expression in pre-invasive lesions suggests immunotherapy is less suitable in the absence of invasion.
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