Dataset Information

PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

ABSTRACT:

Background

The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c⁺ DC co-expressing the immunoinhibitory molecule PD-L1 and their spatial relationship with CD8⁺ T-cells in patients treated for stage III colon cancer.

Methods

Tissue microarrays containing representative cores of central tumor, leading edge, and adjacent normal tissue from 221 patients with stage III colon cancer were immunostained for CD8, CD11c, PD-L1, and cytokeratin using immunofluorescent probes. Cells were quantified using StrataQuest digital image analysis software, with intratumoral and stromal regions analyzed separately. Kaplan-Meier estimates and Cox regression were used to assess survival.

Results

Intratumoral CD8⁺ cell density (HR = .52, 95% confidence interval [CI] .33-.83, P = .007), stromal CD11c⁺ cell density (HR = .52, 95% CI .33-.83, P = .006), intratumoral CD11c⁺ PD-L1⁺ cell density (HR = .57, 95% CI .35-.92, P = .021), and stromal CD11c⁺ PD-L1⁺ cell density (HR = .48, 95% CI .30-.77, P = .003) on leading-edge cores were all significantly associated with good survival. CD8⁺ cell density was positively correlated with both CD11c⁺ cell density and CD11c⁺ PD-L1⁺ cell density in tumor epithelium and stromal compartments.

Conclusion

Here we showed that PD-L1-expressing DC in the tumor microenvironment are associated with improved survival in stage III colon cancer and likely reflect an immunologically "hot" tumor microenvironment. Further investigation into the expression of immunomodulatory molecules by tumor-associated DC may help to further elucidate their prognostic value.

SUBMITTER: Miller TJ

PROVIDER: S-EPMC7935795 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

Miller Timothy J TJ Anyaegbu Chidozie C CC Lee-Pullen Tracey F TF Spalding Lisa J LJ Platell Cameron F CF McCoy Melanie J MJ

Cancer science 20210121 3

<h4>Background</h4>The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c<sup>+</sup> DC co-expressing the immunoinhibitory molecule PD-L1 and their spatial relationship with CD8<sup>+</sup> T-cells in patients treated for stage III colon cancer.<h4>Methods</h4>Tissue microarrays ...[more]

PMID: 33345422

Similar Datasets

Project description:Objectives: We carried out an integrated analysis based on multiple-dimensional types of data from cohorts of bladder cancer patients to identify multi-omics perspective (genomics and transcriptomics) on the tumor microenvironment on the bases of the programmed cell death 1 ligand (PD-L1) and CD8 T-cell infiltration in urothelial carcinoma. Methods: Multiple-dimensional types of data, including clinical, genomic and transcriptomic data of 408 bladder cancer patients were retrieved from the Cancer Genome Atlas database. Based on the median values of PD-L1 and CD8A, the tumor samples were grouped into four tumor microenvironment immune types (TMIT). The RNA sequencing profiles, somatic mutation and PD-L1 amplification data of bladder cancer were analyzed by different TMITs. Results: Our research demonstrated that 36.8% of the evaluated bladder cancer belonged to TMIT I (high PD-L1/high CD8A). TIMT subtypes were not significantly associated with overall survival or disease free survival in urothelial cancer. TMIT I facilitates CD8+ T-cell infiltration and activates T-effector and interferon gamma (IFN-?) associated gene signature. The number of somatic mutations, cytolytic activity, IFN-? mRNA expression and TIGIT mRNA expression in TMIT I was remarkably higher than those in other TMIT groups. Our results showed a high rate of C>T transversion and a high rate of transition/transversion (Ti/Tv) in TMIT I bladder tumors. The RB1 mutation was significantly associated with TMIT I bladder cancer and be significantly co-occurring with the TP53 mutation. However, FGFR3 mutation and TP53 mutation were mutually exclusive in TMIT II bladder tumors. More importantly, different amino acid changes by FGFR3/RB1 mutations were also found between TMIT I and TMIT II bladder cancer, such as amino acid changes in "Immunoglobulin I-set domain (260-356)"and "Protein tyrosine kinase (472-748)". We also detected 9 genes as significantly cancer-associated genes in TMIT I bladder cancer, of which, RAD51C has been reported to play an important role in DNA damage responses. Further analysis concentrated on the potential molecular mechanism found that TMIT I was significantly associated with anti-tumor immune-related signaling pathway, and kataegis was present on chromosome 21 in TMIT I bladder tumors. Conclusions: The classification of bladder cancer into four TMITs on the bases of the PD-L1 expression and the CD8+ CTLs statuses is an appropriate approach for bladder tumor immunotherapy. TMIT I (high PD-L1/high CD8A) is significantly correlated with more somatic mutation burden, and facilitates CD8+ T-cell infiltration and activates T-effector and IFN-? associated gene signature. Alteration landscape for somatic variants was different between TMIT I and TMIT II (low PD-L1/low CD8A).

Dataset Information

PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

Background

Methods

Results

Conclusion

Publications

PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets