Immune responses vary in colorectal cancers, which strongly influence prognosis. However, little is known about the variance in immune response within preinvasive lesions. The study aims to investigate how the immune contexture differs by clinicopathologic features (location, histology, dysplasia) associated with progression and recurrence in early carcinogenesis. We performed a cross-sectional study using preinvasive lesions from the surgical pathology laboratory at the Medical University of South Carolina. We stained the tissues with immunofluorescence antibodies, then scanned and analyzed expression using automated image analysis software. We stained CD117 as a marker of mast cells, CD4/RORC to indicate Th17 cells, MICA/B as a marker of NK-cell ligands, and also used antibodies directed against cytokines IL6, IL17A, and IFNγ. We used negative binomial regression analysis to compare analyte density counts by location, histology, degree of dysplasia adjusted for age, sex, race, and batch. All immune markers studied (except IL17a) had significantly higher density counts in the proximal colon than distal colon and rectum. Increases in villous histology were associated with significant decreases in immune responses for IL6, IL17a, NK ligand, and mast cells. No differences were observed in lesions with low- and high-grade dysplasia, except in mast cells. The lesions of the proximal colon were rich in immune infiltrate, paralleling the responses observed in normal mucosa and invasive disease. The diminishing immune response with increasing villous histology suggests an immunologically suppressive tumor environment. Our findings highlight the heterogeneity of the immune responses in preinvasive lesions, which may have implications for prevention strategies. Prevention Relevance: Our study is focused on immune infiltrate expression in preinvasive colorectal lesions; our results suggest important differences by clinicopathologic features that have implications for immune prevention research.

中文翻译：

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浸润前结直肠病变的免疫反应因肿瘤位置和组织学而异

结直肠癌的免疫反应各不相同，这强烈影响预后。然而，人们对浸润前病变内免疫反应的差异知之甚少。该研究旨在调查与早期癌发生进展和复发相关的临床病理特征（位置、组织学、发育不良）的免疫环境有何不同。我们利用南卡罗来纳医科大学外科病理学实验室的侵袭前病变进行了一项横断面研究。我们用免疫荧光抗体对组织进行染色，然后使用自动图像分析软件扫描和分析表达。我们将 CD117 染色作为肥大细胞的标记，将 CD4/RORC 染色以指示 Th17 细胞，将 MICA/B 染色作为 NK 细胞配体的标记，还使用了针对细胞因子 IL6、IL17A 和 IFNγ 的抗体。我们使用负二项式回归分析按位置、组织学、不典型增生程度比较分析物密度计数，并根据年龄、性别、种族和批次进行调整。研究的所有免疫标志物（IL17a 除外）在近端结肠中的密度计数显着高于远端结肠和直肠。绒毛组织学的增加与 IL6、IL17a、NK 配体和肥大细胞的免疫反应显着降低相关。除肥大细胞外，在低度和高度不典型增生的病变中没有观察到差异。近端结肠的病变富含免疫浸润，与正常粘膜和侵袭性疾病中观察到的反应相似。免疫反应随着绒毛组织学的增加而减弱，表明肿瘤环境具有免疫抑制性。我们的研究结果强调了侵袭前病变中免疫反应的异质性，这可能对预防策略有影响。预防相关性：我们的研究重点是侵袭前结直肠病变中的免疫浸润表达；我们的结果表明临床病理特征存在重要差异，这对免疫预防研究具有影响。