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Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression.


ABSTRACT: Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8+ TILs, higher CD8+/CD4+ ratio, and higher PD-1+ TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer. Of note, PD-L1 expression in tumor cells or immune cells was noted in all cases of CCOCs with MSI. These observations open an alternative therapeutic avenue for a fraction of patients with CCOC and argue for the routine testing of CCOCs for MSI, a test that is not currently routinely performed.

SUBMITTER: Howitt BE 

PROVIDER: S-EPMC5353914 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression.

Howitt Brooke E BE   Strickland Kyle C KC   Sholl Lynette M LM   Rodig Scott S   Ritterhouse Lauren L LL   Chowdhury Dipanjan D   D'Andrea Alan D AD   Matulonis Ursula A UA   Konstantinopoulos Panagiotis A PA  

Oncoimmunology 20170106 2


Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8<sup>+</sup> TILs, higher CD8<sup>+</  ...[more]

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