Prediction of radio-responsiveness with immune-profiling in patients with rectal cancer.

In Ja Park,Seung-Mo Hong,Yun Jae Kim,Sang-Yeob Kim,Chang Sik Yu,Mi-Ju Kim,Soyeon An,Hye Min Lim

doi:10.18632/oncotarget.19558

In Ja Park, Seung-Mo Hong + Show 6 more

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https://doi.org/10.18632/oncotarget.19558

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Abstract

We evaluate whether the tumor immune infiltrate (TIL) could be used for prediction of responsiveness to preoperative chemoradiotherapy (PCRT) in rectal cancers. Using formalin-fixed paraffin-embedded slides of pretreatment biopsies, co-stain for CD4, CD8, CD274 (PD-L1), FOXP3, cytokeratin, and DAPI was performed with Opal multi staining kit (Perkin-Elmer, Waltham, MA). Multispectral imaging and digital analysis to visualize and quantify specific immune infiltrates were performed using the Vectra imaging system (Perkin-Elmer). The density (number of cells per mm2) and proportion of total TILs and specific cell types in the stroma were calculated by inForm™ 2.2.1 software (Perkin-Elmer). The density and proportion of total TILs and specific cell types in the stroma were calculated by inForm™ 2.2.1 software (Perkin-Elmer, Waltham, MA). Patients were classified as group with total regression (TR, n = 25) and group with residual disease (near total, moderate, and minimal regression, RD, n = 50). The mean density of T cell infiltration and CD274 (PD-L1)+ lymphocyte were significantly higher in TR (p = 0.005, p = 0.001). The proportion of CD4+ lymphocyte (p=0.042) and CD274 (PD-L1)+ lymphocyte (p = 0.002) were different between 2 groups. The TR group has lower CD4+ and higher CD274 (PD-L1)+ proportions than RD group. The ratio among CD4+, CD8+, CD274 (PD-L1)+, FOXP3+ T cell was different between groups. TR group showed lower CD4/ CD274 (PD-L1) (p = 0.007), CD8/ CD274 (PD-L1) (p = 0.02), and FOXP3/ CD274 (PD-L1) (p = 0.003) ratio than RD group. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of responsiveness to PCRT.

Highlights

The preoperative chemoradiotherapy (PCRT) was reported to decrease local recurrence, induce tumor down-staging, and allow sphincter preservation [1,2,3] in patients with locally advanced rectal cancer
We evaluate whether the tumor immune infiltrate (TIL) could be used for prediction of responsiveness to preoperative chemoradiotherapy (PCRT) in rectal cancers
We evaluate difference of the immune-infiltrates profiling according to tumor responsiveness to PCRT and how to use immune-infiltrates profiling for prediction of radioresponsiveness in rectal cancer patients

Summary

Introduction

The preoperative chemoradiotherapy (PCRT) was reported to decrease local recurrence, induce tumor down-staging, and allow sphincter preservation [1,2,3] in patients with locally advanced rectal cancer. 12–30% of the patients who received PCRT showed total regression of primary tumor [1, 3, 4]. Patients with total regression to PCRT expected to have good oncologic outcomes [4, 5] and might even have a potential for organpreserving strategy [4, 6]. The clinical and radiological features were disappointing than was expected for predicting responsiveness [7,8,9] researches to search molecular predictors of rectal cancer response www.impactjournals.com/oncotarget to PCRT have been great interest. In addition to genetic alteration, immune components were reported to be associated with PCRT responsiveness as well as oncologic outcome in rectal cancer patients [13]

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