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Poster Presentation
Clinical significance of PD-L1 protein expression on tumor-associated macrophages in lung cancer
  1. Kurt Alex Schalper1,
  2. Daniel Carvajal-Hausdorf1,
  3. Joseph McLaughlin1,
  4. Vamsidhar Velcheti2,
  5. Lieping Chen1,
  6. Miguel Sanmamed1,
  7. Roy S Herbst3 and
  8. David L Rimm1
  1. Aff1 grid.47100.320000000419368710Yale University New Haven CT USA
  2. Aff2 grid.239578.20000000106754725Cleveland Clinic Cleveland OH USA
  3. Aff3 grid.47100.320000000419368710Yale Cancer Center, Yale School of MedicineYale University New Haven CT USA

https://doi.org/10.1186/2051-1426-3-S2-P415

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    Meeting abstracts

    Introduction

    Tumor PD-L1 expression is associated with increased tumor-infiltrating lymphocytes (TILs) in diverse solid tumors, including lung cancer. In addition, PD-L1 upregulation in tumor and/or stromal immune cells has been associated with increased clinical benefit to PD-1/PD-L1 axis blockers. The significance of PD-L1 expression in different immune cell subpopulations at the tumor microenvironment remains poorly understood. Here, we measured PD-L1 protein specifically in tumor-associated macrophages using objective methods and analyzed its clinical significance in human lung cancer.

    Methods

    Using multiplexed quantitative immunofluorescence (QIF) we measured the levels of PD-L1 protein (clone-E1L3N, Cell Signaling technology) in 554 stages I-IV FFPE lung carcinomas represented in two tissue-microarrays, one from Yale University [YTMA79, n=204] and one from Greece [YTMA140, n=350]. PD-L1 was measured using multispectral QIF in CD68-positive cells (macrophages, clone-KP1, DAKO) or in tumor cells (clone-AE1/AE3, DAKO) based on fluorescence co-localization. The levels of CD3 (T cells, clone-E272, Novus), CD8 (cytotoxic T cells, clone-C8/144B, DAKO) and CD20 (B-lymphoctes, clone-L26, DAKO) were also determined in the tumor samples. Associations between the macrophage and tumor PD-L1 levels, clinico-pathological variables and survival were analyzed.

    Results

    In lung cancer samples, PD-L1 was detected in both macrophages and tumor cells with a predominant membranous staining pattern. Overall, the levels of PD-L1 in the CD68+ population were lower than in tumor cells in both cohorts (834 ± 314 AU vs 1113 ± 427 AU, in the Yale cohort, P < 0.001; and 895 ± 451 AU vs 1069 ± 542 AU in the Greek set, P < 0.001). In both collections, the macrophage and tumor PD-L1 signal showed a positive non-linear association (Linear regression coefficient [R2]=0.311 in the Yale cohort and R2=0.43 in the Greek collection). Using the median score as cutpoint, elevated macrophage PD-L1 content was significantly associated with high CD8+ and CD20+ cells in both cohorts. In addition, increased macrophage PD-L1 signal was marginally associated with longer overall survival in the Yale set (HR=0.676 [CI:0.450-1.081], P=0.05), but not in the Greek group (HR=0.790 [CI:0.560-1.109], P=0.17).

    Conclusion

    PD-L1 is expressed in tumor-associated macrophages of human lung carcinomas. The macrophage PD-L1 signal is lower than in tumor epithelial cells and they show a positive association. Elevated macrophage PD-L1 is prominently associated with increased cytotoxic T lymphocytes and B cell infiltrates in lung tumors, but has limited prognostic value. Further studies will be required to evaluate the possible predictive role of PD-L1 expression in macrophages and other immune cell types.