Dataset Information

Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II-III colorectal cancer.

ABSTRACT: Programmed cell death-1 (PDCD1/PD-1) and its ligand programmed cell death 1 ligand 1 (CD274/PD-L1) have been reported to suppress anti-tumor T cell-mediated immune responses. However, the clinical significance of CD274 in colorectal cancer were still elusive. We aim to clarify the relationships between CD8+ intratumor-infiltrating lymphocytes (TILs) and CD274 as well as their prognostic values in stage II-III colon carcinoma. Tumor differentiation, perineural invasion (PNI), pN stage and DNA mismatch repair (MMR)-deficient were clearly correlated with CD8+ TILs counts within the tumor microenvironment (p < 0.0001). Furthermore, tumor differentiation and PNI were suggestively correlated with tumor CD274 expression (p = 0.02 and p = 0.0195). Tumor CD274 level was significantly correlated with higher CD8+ TILs (p < 0.0001) but was not associated with MMR-deficient status (p = 0.14). High tumor CD274 expression [hazard ratio (HR) = 2.16, 95% CI = 1.63-2.86, p < 0.0001] and CD8+ TILs [HR = 1.51, 95% CI = 1.19-1.91, p = 0.0007] were associated with improved disease-free survival and overall survival. Additionally, the subgroup of patients who had a high CD8+ TILs/tumor CD274 have better survival outcomes compared with other subgroups (71% vs 53%; p < 0.0001). Therefore, the CD8+ TILs counts and tumor CD274 may be prognostic factors to predict survival and therapeutic responses in stage II-III colon carcinoma patients.

SUBMITTER: Huang CY

PROVIDER: S-EPMC6199287 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II-III colorectal cancer.

Huang Chih-Yang CY Chiang Shu-Fen SF Ke Tao-Wei TW Chen Tsung-Wei TW You Ying-Shu YS Chen William Tzu-Liang WT Chao K S Clifford KSC

Scientific reports 20181023 1

Programmed cell death-1 (PDCD1/PD-1) and its ligand programmed cell death 1 ligand 1 (CD274/PD-L1) have been reported to suppress anti-tumor T cell-mediated immune responses. However, the clinical significance of CD274 in colorectal cancer were still elusive. We aim to clarify the relationships between CD8+ intratumor-infiltrating lymphocytes (TILs) and CD274 as well as their prognostic values in stage II-III colon carcinoma. Tumor differentiation, perineural invasion (PNI), pN stage and DNA mis ...[more]

PMID: 30353144

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Project description:BackgroundCholangiocarcinoma (CCA) may arise in the intra- or extrahepatic biliary tract and is associated with a poor prognosis. Despite recent advances, to date there is still no established targeted therapeutic approach available. Non-surgical therapeutic agents are urgently needed, as most patients are non-eligible to surgical resection. Anti-PD-L1 therapy prevents cancer cells from evading the immune system and has emerged as a new treatment option in several cancer entities. Recently, PD-L1 expression has been analyzed in comparably small CCA patient cohorts. However, a systematic validation of different PD-L1 antibodies has not been performed in CCA so far.MethodsWe stained a tissue microarray consisting of 170 patients, including 72 intrahepatic cholangiocarcinomas (iCCAs), 57 perihilar cholangiocarcinomas (pCCAs) and 41 distal cholangiocarcinomas (dCCAs) by immunohistochemistry and evaluated PD-L1 positivity in tumor and stromal cells. We analyzed three different PD-L1 antibodies (clones 28-8, SP142, and SP263) that are frequently used and recommended for predictive diagnostic testing in other cancer types.ResultsFor PD-L1 antibody clone SP263, 5% of iCCAs, 4% of pCCAs and 3% of dCCAs exhibited PD-L1 expression on tumor cells, thereby showing the highest frequencies of PD-L1 positivity. Accordingly, highest PD-L1 positivity rates of stromal cells with 31% in iCCA, 40% in pCCA and 61% in dCCA were detected for clone SP263. Agreement of PD-L1 positivity in tumor cells was moderate for clone 28-8 and SP263 (κ = 0.44) and poor between 28-8 and SP142 (κ = 0.13), as well as SP142 and SP263 (κ = 0.11), respectively. Statistical analyses of PD-L1 expression (clone SP263) on tumor cells with clinicopathological data revealed a positive correlation with shortened overall survival in CCA patients.ConclusionsSelection of appropriate PD-L1 antibodies and careful evaluation of immunohistochemical staining patterns have a significant impact on PD-L1 testing in CCA. Clinical trials are necessary to investigate the putative beneficial effects of PD-L1 targeted immunotherapy in CCA patients.

Project description:Objectives: Thymic epithelial tumors (TETs) are rare malignant tumors that exhibit heterogeneous histology and clinical behavior. As immune check point inhibitors, drugs targeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown remarkable results against many cancers; thus, the importance of PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker has grown. However, limited data on PD-L1 and PD-1 expression in TETs have been reported; moreover, these results have been variable. Here, we examined the expression of PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance of this expression. Patients and Methods: A tissue microarray was constructed using 368 samples of TETs, each in triplicate. Immunohistochemistry for PD-L1 (SP263 assay) and PD-1 in TETs and CD8 in thymic carcinoma (TC) was performed; next, correlations with clinicopathologic characteristics were analyzed. PD-L1high was designated as ≥50% of tumor proportion score; PD-1high and CD8high were defined as ≥5% and 1% of tumoral immune cells, respectively. Results: The cohort consisted of 308 patients with thymomas and 60 patients with TC. PD-L1 positivity was identified in 90.6% (328/362, ≥1%) of TETs, PD-1 expression of intra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivity was identified in 11% (7/60, ≥1%) of TC. Of the 362 patients, 141 (39.0%) exhibited high PD-L1 expression (PD-L1high). The PD-L1high thymoma group was correlated with high Masaoka-Koga stage (p < 0.001), type B3 histology (p < 0.001), and myasthenia gravis (p < 0.001). This group exhibited poor overall survival (OS, p = 0.003, log-rank) and worse disease-free survival (DFS, p = 0.042, log-rank). No survival differences were detected between PD-L1high and PD-L1low groups in TC. Additionally, there was no correlation between PD-1 expression and survival in patients with TETs. Multivariate analysis revealed that PD-L1high expression was an independent poor prognostic factor (p = 0.047, HR 2.087, 95% CI, 1.009-4.318) in thymomas. Conclusions: To our knowledge, this is the largest study on TETs published in English literature. This study provides useful information regarding the prognosis of and potential therapeutic options for patients with TETs.

Dataset Information

Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II-III colorectal cancer.

Publications

Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II-III colorectal cancer.

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