由於不同癌症類型之間腫瘤免疫微環境和臨床實踐差異，針對特定藥物、特定適應症的PD-L1 IHC檢測體系和PD-L1表達評估判讀方法往往需要經過前瞻性臨床試驗驗證，以確保最終潛在治療獲益患者篩選的準確性[5][7][8]。因此，臨床實踐中PD-L1 IHC標準檢測往往涉及藥物註冊試驗驗證的整個檢測體系，目前已商業化PD-L1 (SP263)檢測為50測試數即用型檢測，臨床獲批檢測體系包括VENTANA OptiView DAB二抗系統和BenchMark全自動染色平台[1][5][9]。
染色性能方面，基於SP263兔單克隆抗體抗原定位特點，PD-L1 (SP263)對腫瘤組織顯色模式以細胞膜和/或細胞漿染色為主[2-5]。由於腫瘤組織免疫微環境時空連續性特點（基於器官和區域表達以及不同階段動態變化導致的差異性），不同癌症類型中PD-L1表達評估或涉及腫瘤細胞和/或免疫細胞[4][5 ][7] [8]，例如肺癌PD-L1 (SP263)評估主要以腫瘤細胞染色為主，而尿路上皮癌則同時涉及腫瘤細胞和免疫細胞染色評估(如圖1. ) [8][ 10][11]。
圖1. PD-L1 (SP263)抗體檢測試劑（IHC）腫瘤組織染色研髮染色性能評估（基於OptiView DAB二抗系統和BenchMark全自動染色平台），Section 2, Section 25, Section 50為評估研究部分PD -L1 IHC染色示例，NSCLC (非小細胞肺癌), HNSCC (頭頸部鱗狀細胞癌), UC (尿路上皮癌)腫瘤組織各三個切片，腫瘤細胞(TC)和免疫細胞(IC) PD-L1 (SP263)檢測染色評分由經培訓病理學家進行評估。（鏡下放大倍數：NSCLC: ×4; HNSCC: ×2; UC: ×10）[10][11]
SP263標準檢測體系之臨床研究盤點
基於Keynote024 [17]、Keynote010 [18]和CheckMate057 [19]以及AZ comparison study研究[20]結果，PD-L1 (SP263)檢測體系先後於CE IVD認證獲批用於帕博利珠單抗和納武利尤單抗非小細胞肺癌相關適應症PD-L1表達評估[3][11][12]。基於Pacific研究[21][22]中試驗驗證結果，獲批用於德瓦魯單抗非小細胞肺癌相關適應症PD-L1表達評估[3][11][12]。
從臨床試驗驗證和法規批准兩個維度整體而言，截至發稿日，PD-L1 (SP263)檢測體系在全球範圍已獲批PD-L1 IHC標準檢測體系中用於評估PD-L1表達相關聯藥物尚居榜首[3][12][13]。
表1. PD-L1 (SP263)檢測臨床註冊研究及適應症信息匯總[1][3][11-13]
一致性與室間質控評估
至此，如前文所述，SP263檢測體係也已獲批NSCLC相關4款和UC相關2款PD-1/PD-L1抑製劑相應適應症標準PD-L1 IHC檢測[1][3][11- 13]。目前的證據表明，PD-L1 IHC判讀評分和藥物以及癌症類型之間或存在顯著差異，SP263檢測體系在不同藥物臨床試驗和一致性評價研究中的表現或提示PD-L1 IHC檢測體系標準化仍在一定程度上能實現互換、可及[5][12]。
雖然大量研究嘗試進一步探究和評價不同免疫治療相關標誌物，但通過PD-L1 IHC檢測預測性分析目前或未來仍是多種癌症類型治療決策指導的標準檢測。因此，在現階段進一步提升病理實驗室PD-L1 IHC檢測體系標準建設和判讀培訓教育、確保准確的PD-L1診斷結果，對於識別最有可能受益於PD-1/PD-L1免疫治療患者仍至關重要。
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