Vycital Ondrej, Dubova Magdalena, Palek Richard, Hosek Petr, Branzovsky Jindrich, Treska Vladislav, Daum Ondrej, Liska Vaclav
Department of Surgery, Medical School and Teaching Hospital Pilsen, Charles University, Pilsen, Czech Republic
Biomedical Centre, Medical School and Teaching Hospital Pilsen, Charles University, Pilsen, Czech Republic.
Anticancer Res. 2018 Jul;38(7):4159-4167. doi: 10.21873/anticanres.12709.
BACKGROUND/AIM: Tumour-infiltrating lymphocytes (TILs) and Granzyme B play crucial roles in immune reactions against colorectal carcinoma (CRCa). The inhibitor of Granzyme B is Serpin B9. The aim of this study was to evaluate the effect of immunohistological parameters of TILs on the prognosis of CRCa and presence of lymph node metastasis.
A total of 152 patients who underwent surgery for CRCa were analyzed, including 63 patients in cohort stage II, according to the Union for International Cancer Control (UICC), and 89 patients in cohort UICC stage III. The TIL pattern was classified as peritumoural (PTL), intratumoural (ITL), intrastromal (ISL) or Crohn-like, and immunohistological staining of TIL and cancer cells was also performed.
A significantly higher density of CD8 and CD4 TILs was observed in the UICC II group, and significantly higher densities of CD4 TILs were observed in the UICC II group in all distinguished patterns. In the same cohort, higher numbers of CD57 cells and FoxP3 TILs and Granzyme B levels were observed. In cohort UICC III, there was a higher density of ISL, PTL CD8, CD25 TILs and cancer cells showed staining for Serpin B9. CD57, Granzyme B and CD8 were demonstrated as positive prognostic factors of overall survival, and CD57 and CD4 TILs were demonstrated as positive prognostic factors of recurrence.
TILs and CD57 are promising prognostic factors of CRCa. The association of Serpin B9 with lymph node metastasis reveals a potential mechanism for tumour resistance to immune reaction.
背景/目的：肿瘤浸润淋巴细胞（TILs）和颗粒酶B在针对结直肠癌（CRCa）的免疫反应中发挥关键作用。颗粒酶B的抑制剂是丝氨酸蛋白酶抑制剂B9（Serpin B9）。本研究的目的是评估TILs的免疫组织学参数对CRCa预后及淋巴结转移情况的影响。
根据国际癌症控制联盟（UICC）标准，共分析了152例行CRCa手术的患者，其中II期队列患者63例，III期队列患者89例。TIL模式分为瘤周（PTL）、瘤内（ITL）、基质内（ISL）或克罗恩样，同时对TIL和癌细胞进行免疫组织学染色。
UICC II组观察到CD8和CD4 TILs密度显著更高，在所有区分的模式中，UICC II组CD4 TILs密度也显著更高。在同一队列中，观察到CD57细胞、FoxP3 TILs数量及颗粒酶B水平更高。在UICC III期队列中，ISL、PTL CD8、CD25 TILs密度更高，癌细胞显示有Serpin B9染色。CD57、颗粒酶B和CD8被证明是总生存的阳性预后因素，CD57和CD4 TILs被证明是复发的阳性预后因素。
TILs和CD57是CRCa有前景的预后因素。Serpin B9与淋巴结转移的关联揭示了肿瘤对免疫反应产生抗性的潜在机制。
