• Checkpoint Inhibitors for Ophthalmic Sebaceous Carcinoma

    By Jean Shaw
    Selected By: Richard K. Parrish II, MD

    Journal Highlights

    American Journal of Ophthalmology, December 2020

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    Immune checkpoint inhibitors (ICIs), which block the programmed death 1 (PD-1) receptor and its ligands, PD-L1 and PD-L2, are not routinely used for ocular adnexal malignancies. How­ever, a handful of recent reports have described the successful use of ICIs in patients with advanced ocular adnexal sebaceous carcinoma (OASC). Wolkow et al. set out to evaluate the expression of PD-L1 and PD-L2 in patients with OASC and to assess whether the results support the use of ICIs. They confirmed that PD-L1 and PD-L2 are expressed in a high percentage of OASC cases, and they noted that the results support the premise that ICIs hold therapeutic promise for these patients.

    For this retrospective study, the researchers immunostained 20 cases of primary OASC for PD-L1, PD-L2, and the lymphocyte CD8. They used the combined positive score (CPS) and the tumor proportion score (TPS) to grade PD-L1 and PD-L2 expression, and they graded CD8 expression on a 0-3 scale. They then compared the results with those of similar recent investigations.

    For the 20 cases, mean expression of PD-L1 with the CPS was 29.7 (range, 0-101.5) and 12.2 with the TPS (range, 0-95.8). Mean expression of PD-L2 was 7.9 with the CPS (range, 0-37.3) and 1.9 with the TPS (range, 0-12.9). His­tologic results indicated that 19 (95%) and 17 (85%) of the samples expressed some degree of PD-L1 with the CPS and TPS, respectively. In contrast, 13 (65%) and four (20%) of the samples expressed some degree of PD-L2 with the CPS and TPS, respectively. All 20 cases had CD8-positive T lymphocytic infiltrates, with a mean ± standard deviation of 1.75 ± 0.72, and significant correlations were observed between tissue expression of PD-L1, PD-L2, and CD8.

    In analyzing four other studies, the researchers found similar results. They also summarized reported positive out­comes of OASC patients treated with ICIs. As a result, they conclude, “there is now a pressing and inescapable rationale for the implementation of ICI drugs in clinical trials, particularly at advanced stages of OASC.”

    The original article can be found here.