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Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering. Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies. Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones.

SUBMITTER: Ribbat-Idel J

PROVIDER: S-EPMC8110724 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking.We assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients.A significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient's outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases.In summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.In spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1. Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.

Project description:IntroductionImmune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study's main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings.Materials and methodsThis is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies.ResultsWe analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65-0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity.Discussion and conclusionsOur data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.

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Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma.

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