Tissue-infiltrating lymphocytes signature predicts survival in patients with early/intermediate stage hepatocellular carcinoma

Abstract

Background Intratumoral immune infiltrates have manifested a robust prognostic signature in patients with hepatocellular carcinoma (HCC). We hypothesized that a novel tissue-related immune signature (TRIS) could improve the prediction of postoperative survival for patients diagnosed with early/intermediate HCC. Methods Twenty-eight immune features were immunohistochemically examined on 352 HCC specimens. The LASSO Cox regression model was used to construct a five-feature-based TRIS. The univariate and multivariate Cox analyses were performed. Based on independent predictors, the immune-clinical prognostic index (ICPI) was established. Performance assessment was measured with C-index and compared with seven traditional staging systems. The independent validation cohort ( n = 393) was included to validate the model. Results By using the LASSO method, the TRIS were constructed on the basis of five immune features, CD3 intratumoral (T) , CD27 T , CD68 peritumoral (P) , CD103 T , and PD1 T . Multivariate Cox analysis showed that the TRIS was an independent prognostic predictor. In the training cohort, γ-glutamyl transferase, tumor diameter, tumor differentiation, and TRIS were incorporated into the ICPI. The ICPI presented satisfactory discrimination ability, with C-index values of 0.691 and 0.686 in the training and validation cohorts, respectively. Compared with seven conventional staging systems (C-index, training cohort, 0.548–0.597; validation cohort, 0.519–0.610), the ICPI exhibited better performance for early/intermediate-stage HCCs. Further, the patients were categorized into three subgroups with X-tile software, and the stratified ICPI presented a superior corrected Akaike information criterion and homogeneity in both cohorts. Conclusions Our ICPI was a useful and reliable prognostic tool which may offer good individualized prediction capability for HCC patients with early/intermediate stage. Electronic supplementary material The online version of this article (10.1186/s12916-019-1341-6) contains supplementary material, which is available to authorized users.

Prediction of overall survival in resectable intrahepatic cholangiocarcinoma: ISICC‐applied prediction model

“…Tissue microarray (TMA) construction was performed as previously described . Briefly, two representative areas with infiltrating lymphocytes were selected on H&E‐stained slides.…”

“…Duplicate cores (2 μm in diameter) were taken, arrayed and re–embedded from tumor and peritumor regions. Fourteen monoclonal and two polyclonal antibodies against CD3, CD4, CD8, CD14, CD20, CD27, CD45RO, CD45RA, CD57, CD66b, CD68, CD103, Foxp3, CXCR5, PD‐L1 and PD1 were used for staining, as reported previously . To evaluate peritumoral and intratumoral infiltrating immune cells, the three most representative and independent fields were selected and photographed at ×200 magnification.…”

“…Identical settings were used for each photograph. The numbers of positive cells were counted and recorded using a computer‐automated method (Image‐Pro Plus 6.0, Media Cybernetics) as previously described . Figure presents the spot and the captured spot (×200) with image software.…”

Development of an Immune Infiltration-Related Prognostic Scoring System Based on the Genomic Landscape Analysis of Glioblastoma Multiforme

“…LASSO Cox analysis, as a wildly used high-dimensional predictor regression method (18), selecting the optimal penalty parameter lambda using 10-fold cross-validations to prevent overfitting (19), can achieve shrinkage and variable identify simultaneously (20), and thus, which is an appropriate solution to establish signatures if there are numerous correlated covariates (21). Therefore, we utilized LASSO Cox regression analysis in the training set to establish an IIRPSS by a linear combination of selected prognostic cell compositions among 22 immune cell types weighted by the optimal coefficients.…”

Tumor-infiltrating immune cells signature predicts recurrence free survival after complete resection of localized primary gastrointestinal stromal tumors

“…An international multi-nation corporation of 14 centers assessed the the immunoscore based on the amounts of CD3+ and CD8+ T cells in TNM stage I-III colon cancer, and finally proved that the immunoscore provided the highest relative contribution to the risk of recurrence in colon cancer. 13 The proposal and effectiveness of the immunoscore has been validated in several other cancers such as gastric cancer, 14 hepatocellular carcinoma 15 , urothelial carcinoma of the bladder 16 and so on. These existing evidence indicated that immunoscore provides a more accurate prognosis.…”