Immunoprofiling of Colitis-associated and Sporadic Colorectal Cancer and its Clinical Significance

Abstract

Immunoprofiling is useful for predicting prognosis in various malignancies and provides targets for immunotherapy. Quantitative multispectral imaging system, which allows simultaneous detection of multiple immune markers, is a novel method for examining the tumor immune environment. We compared the expression levels of various surface markers in immune cells between colitis-associated cancer (CAC) and sporadic colorectal cancer (CRC) and evaluated the clinical usefulness of immunoprofiling in CRC. Tumor specimens from 24 CAC patients and 48 sporadic CRC patients, matched by age, sex, and tumor location to CAC, were included in the analysis. The expression levels of CD3, CD8, Foxp3, and programmed death-ligand 1 (PD-L1) in immune cells at the invasive margins of tumor tissues were evaluated by quantitative multispectral imaging. The CAC group had significantly less levels of cells expressing CD3, CD8, Foxp3, or PD-L1 (all, p < 0.01). In the CAC group, patients whose immune cells had high expression of CD3 + and CD8 + had better overall survival. The immune profiling patterns of CAC patients were significantly distinct from those of sporadic CRC patients, suggesting that CAC and sporadic CRC have distinct disease phenotypes. Immunoprofiling can be helpful for evaluation of clinical prognosis in CAC.

Application of Immunoprofiling Using Multiplexed Immunofluorescence Staining Identifies the Prognosis of Patients with High-Grade Serous Ovarian Cancer

“…The primary antibodies and corresponding TSA used for each protein were as follows: anti-CK (AE1/AE3, M3515, Dako, CA, USA) and Opal 520 for CK, anti-PD-L1 (E1L3N, #13684, Cell Signaling, Danvers, MA, USA) and Opal 540 for PD-L1, anti-CD20 (L26, ab133616, Leica, Wetzlar, Germany) and Opal 570 for CD20, anti-CD4 (EPR6855, NCL-L-CD20-L26, Abcam, Cambridge, MA, USA) and Opal 620 for CD4, anti-CD8 (4B11, NB100-65729, Novusbio, Centennial, CO, USA) and Opal 650 for CD8, and anti-FoxP3 (236A/E7, ab20034, Abcam, Cambridge, MA, USA) and Opal 690 for FoxP3. The methods have been introduced in detail in previous studies [32,33].…”

TLR9 induces colitis‑associated colorectal carcinogenesis by regulating NF‑&kappa;B expression levels

“…The majority of these studies primarily focused on the role of TLR9 in colitis or sporadic CRC, whereas the current study focused on the role of TLR9 in the pathogenesis of CAC to provide novel targets for the treatment of CAC. For example, alterations in microtubule end-binding protein 1 were identified as a characteristic of sporadic, but not UC-associated CRC ( 46 ), and in another previous study, the immune profiling patterns of patients with CAC were significantly different compared with the patients with sporadic CRC ( 47 ).…”

Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer

“…Considering that the difference between these CD4 + subsets is not detectable by conventional IHC, our multiplexed approach enhanced the quality of the analysis. This novel quantitative multispectral imaging method has been validated to reflect conventional IHC-based immune cell evaluation [ 29 ] and is increasingly used to assess the immune profiles of the TME [ 30 ]. Its clinical usefulness deserves further investigation in future studies dealing with various immune subsets and clinical settings.…”