Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer

Ino, Y; Yamazaki-Itoh, Rie; Shimada, Kazuaki; Iwasaki, Mariko; Kosuge, Tomoo; Kanai, Yae; Hiraoka, Nobuyoshi

doi:10.1038/bjc.2013.32

Cited by 741 publications

(741 citation statements)

References 32 publications

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“…A negative prognostic impact of tumor-infiltrating regulatory T cells has been shown for several types of cancer, including gastric cancer. [46][47][48][49][50][51][52][53] The comprehensive mutational analysis in this study is in concordance with the findings of other studies. 54 That we could not find a correlation between the genomic profile and expression of immune checkpoint receptors is probably due to the low frequencies of the analyzed mutations.…”

Section: Cd25supporting

confidence: 92%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

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Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted nextgeneration sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumordraining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/ 127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment.Abbreviations: CTLA-4, cytotoxic T lymphocyte associated molecule 4; PBMC, peripheral blood mononuclear cells; PD-1, programmed death 1; PD-L1, programmed death 1 ligand 1; TDLN, tumor-draining lymph nodes; UICC, Union International Contre le Cancer.

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Section: Cd25supporting

confidence: 92%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

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“…Three areas with abundant CD8 + T-cells in cancer cell nests and three areas with many CD163 + macrophages in tumor stroma around cancer cells were selected at a magnification of ×100 (13,14). Stroma areas where CD163 + macrophages were recruited as a result of necrosis, bleeding and destruction of tubular glands were not selected.…”

Section: Evaluation Of Immunohistochemistrymentioning

confidence: 99%

“…Cluster of differentiation (CD) 163 was shown to be useful marker for M2-like macrophages in patients with intrahepatic cholangiocarcinoma (11). In pancreatic cancer, high numbers of infiltrating CD163 + macrophages in tumor stroma are a poor prognostic indicator (12,13).…”

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confidence: 99%

Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer

Miura¹,

Yoshizawa²,

Hirai³

et al. 2017

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Abstract. Aim: The aim of this study was to examine the clinicopathological influence of tumor-infiltrating cluster of differentiation (CD) 163 + macrophages and CD8 + T-cells, and to clarify the prognostic effects of these cells in patients with invasive extrahepatic bile duct cancer (EHBC). Materials and Methods: The numbers of CD8 + T-cells in cancer cell nests and CD163 + macrophages in tumor stroma (hazard ratio=0.127, p<0.001) and in patients treated with adjuvant chemotherapy (hazard ratio=0.139, p=0

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“…The stroma is composed of myofibroblasts, endothelial cells, pericytes, and immune cells along with its extracellular matrix (ECM). [15] It is a highly fibrotic tumor, and this fibrotic environment allows the tumor to grow rapidly and be relatively impermeable to systemic chemotherapy. The unique nature of the tumor presents clinicians with difficult obstacles to overcome.…”

Section: Established Risk Factors and High Risk Of Recurrencementioning

confidence: 99%

Emerging therapies for pancreatic ductal carcinoma

Falcone

Davis

Stain

et al. 2016

JST

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Pancreatic ductal adenocarcinoma (PDAC) is a solid tumor mass that grows and metastasizes rapidly. There are no definitive methods for early detection and most patients are diagnosed at a late stage. Those diagnosed at an early stage are eligible for tumor resection. However, many of these patients are soon burdened with tumor recurrence. The tumor grows back aggressively and with resistance to the original chemotherapy. Gemcitabine has been the treatment of choice, but provides only minimal survival prolongation. Researchers are trying to improve the current standard of care by finding different methods to improve treatment efficacy and reduce side effects. This review emphasizes recent data on targeting the tumor using antifibrotic, nanotargeted, and dendritic cell therapies. Antifibrotic therapy aims to reduce tumor fibrosis, which prevents adequate chemotherapy penetration. Nanotargeted therapy offers precise targeting of cancer cells and chemotherapy delivery. Dendritic cell vaccines stimulate the body's immune system to target PDAC cells. These three treatment methods or a combination of them might improve the lifespan and quality of life for PDAC patients.

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Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer

Cited by 741 publications

References 32 publications

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer

Emerging therapies for pancreatic ductal carcinoma

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