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PD ‐L1 and IDO expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for combination immunotherapy
Author(s) -
Chinn Zachary,
Stoler Mark H,
Mills Anne M
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13723
Subject(s) - vulvar intraepithelial neoplasia , medicine , immunohistochemistry , cervical intraepithelial neoplasia , immunotherapy , intraepithelial neoplasia , human papillomavirus , vulva , hpv infection , oncology , cancer research , pathology , immunology , immune system , cervical cancer , cancer , prostate
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 SCC s were significantly more likely than human papillomavirus ( HPV )‐related vulvar SCC s 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 SCC s and, to a lesser extent, vulvar SCC s. These data suggest a role for combination immunotherapy in a subset of cervical SCC s as well as select vulvar SCC s. Expression for both markers is less common in intraepithelial lesions, providing no strong support for this form of immunotherapy in the absence of invasion.