结直肠癌中PDL-1表达与肿瘤出芽及浸润淋巴细胞的关系

Tejasvita Singh, Anshul Singh, Manoj Bind, V. Misra, S. Misra, M. Dwivedi, Shabir Ahmad
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摘要

目的:探讨PDL-1在结直肠癌中表达与肿瘤出芽及浸润淋巴细胞的关系。背景:结直肠癌(CRC)是第三大常见癌症,死亡率高。为了提高结直肠癌患者的总生存率,人们做了许多尝试。免疫系统在清除不健康的癌细胞方面起着重要的作用。程序性死亡1 (PD1)是一种调节分子,当与它的一个互补配体(PDL1)结合时,它会抑制免疫反应。它的表达与免疫治疗在结直肠癌治疗中的反应有关,近年来已被开发。然而,其预后价值仍存在争议,PD-L1在肿瘤细胞或免疫细胞上的分布尚未得到全面分析。方法:共纳入30例诊断为crc的患者,并行手术干预。术前接受新辅助化疗或放疗者排除在外。对PDL1进行免疫组化分析,并与肿瘤出芽和肿瘤浸润淋巴细胞(til)相关,并评估统计学意义。结果:11例有创前芽数低,其中仅有3例PDL1阳性。其余19例芽数较高,其中18例为PDL 1阳性。这一差异非常显著(p = 0.002)。在低芽/高芽组中,75%的病例肿瘤细胞中没有PDL1表达,而62.5%的病例肿瘤细胞中PDL1表达阳性,而在高芽/低芽组中,所有病例(100%)肿瘤细胞中PDL1表达,而只有75%的病例肿瘤细胞中PDL1表达阳性,同样具有统计学意义(p <0.001)。结论:本研究显示肿瘤芽中PDL1与免疫细胞呈负相关,强调肿瘤微环境的作用。我们的研究重申了肿瘤细胞中PDL1的高表达会抑制抗肿瘤反应,而其在TILS中的高表达与更好的预后相关。
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Correlation of PDL-1 Expression with Tumour Budding and Tumour Infiltrating Lymphocytes in Colorectal Cancers
Objective: To study and correlate PDL-1 expression with Tumour budding and Tumour Infiltrating Lymphocytes in Colorectal Carcinoma. Background: Colorectal cancer (CRC) is third most common cancer with a high mortality. Many attempts have been made to raise overall survival of CRC patients. The immune system plays an important role in clearing the unhealthy cancer cells. Programmed death 1 (PD1) is a regulatory molecule which dampens the immune response when bound to one of its complementary ligands (PDL1). Its expression is related to the response of immunotherapy in CRC treatment which has been exploited in recent times. However, its prognostic value is still controversial, and the distribution of PD-L1 on tumour Cells or Immune Cells has not been comprehensively analysed. Method: A total of 30 patients diagnosed with CRCs were included who underwent surgical intervention. Cases who took preoperative neoadjuvant chemotherapy or radiotherapy were excluded. IHC analyses of PDL1 was done and was correlated with tumour budding and Tumour Infiltrating Lymphocytes (TILs) and statistical significance was assessed. Results: 11 cases showed low bud count at the invasive front out of which only 3 cases showed PDL1 positivity. The rest 19 cases had high bud count out of which 18 were PDL 1 positive. This difference was highly significant (p = 0.002). In Low Bud / High TILs, 75% cases showed no PDL1 expression in tumour cells, whereas 62.5% cases showed PDL1 positivity in TILs whereas in High Bud / Low TILs group, all the cases (100%) showed PDL1 expression in tumour cells whereas only 75% cases showed PDL1 positivity in TILs, again being statistically significant (p <0.001). Conclusion: This study showed an inverse correlation between PDL1 in tumour buds and immune cells, thus emphasising the role of tumour microenvironment. Our study reiterates the fact that high expression of PDL1 in tumour cells suppresses antitumor response whereas its high expression in TILS correlates with a better prognosis.
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