Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis

Charbel, Alphonse; Tavernar, Luca; Albrecht, Thomas; Brinkmann, Fritz; Verheij, Joanne; Roos, Eva; Vogel, Monika; Köhler, Bruno; Springfeld, Christoph; Brobeil, Alexander; Schirmacher, Peter; Singer, Stephan; Mehrabi, Arianeb; Roessler, Stephanie; Goeppert, Benjamin

doi:10.1038/s41416-022-01933-0

Cited by 4 publications

(3 citation statements)

References 58 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A growing body of evidence suggests that TME, including cancer cells and immune cells, supports tumor growth and evasion [24,25] . Several studies have identified the critical task performed by the ectonucleotidase CD39 in generating this immunosuppressive environment [26,27] .…”

Section: Discussionmentioning

confidence: 99%

Heterogenous distribution of PD-1+CD39+CD8+ T cell in TME defined its immunotherapeutic biomarker in lung cancer

Zhai

Zhang

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

CD8+ T cells in tumors are heterogenous and exist in multiple differentiation states. Evidence has proposed CD39 as a marker of exhausted and tumor-reactive CD8+ T cells. Here, we analyzed a subset of tumor-infiltrating CD8+ T cells based on the expression of the immunosuppressive ATP ectonucleotidase CD39 and PD-1. Neoplasm-superficial biopsy and intratumoral EBUS-TBNA were used to assess the peripheral and central tumor microenvironment, respectively. CD39+CD8+ T cells dominantly accumulated in the peritumoral compartment of larger tumors and exhibited an exhausted phenotype compatible with PD-1 expression. Compared with CD39+CD8+ T cells, PD-1+CD39+CD8+ T cells are better biomarkers for predicting responses to anti-PD-1 therapy. Collectively, heterogenous distribution may be critical to elicit CD39 expression in lung cancer associated CD8+ T cells. Increased PD-1+CD39+CD8+ T cell levels within the peripheral TME can act as a candidate biomarker for lung cancer immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Heterogenous distribution of PD-1+CD39+CD8+ T cell in TME defined its immunotherapeutic biomarker in lung cancer

Zhai

Zhang

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Accumulating evidence suggests that TME, including cancer cells and immune cells, supports tumor growth and evasion (19,20) . Several studies have pointed to the critical task carried out by CD39 in generating this immunosuppressive environment (21,22) .…”

Section: Discussionmentioning

confidence: 99%

Spatial distribution of PD-1+CD39+CD8+ T cell in TME refined its tumorigenic and immunotherapeutic biomarker in lung cancer

Zhai

Zhang

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose CD8 + T cells in tumors are heterogenous and comprise multiple differentiation states. It has been reported that human tumor-infiltrating CD8 + T cells can express CD39 and more evidences proposed CD39 as a marker of exhausted and tumor reactive CD8 + T cells. However, no studies have delved into the spatial distribution of the CD39 + CD8 + T cell subsets in lung cancer, which could help to evaluate the immune microenvironment for developing the future immunotherapy approaches. Methods A total of 53 lung cancer patients prior to any therapy were included. A subset of tumor-infiltrating CD8 + T cells marked by expression of the immunosuppressive ATP ecto-nucleotidase CD39 and PD-1 was analyzed. Neoplasm-superficial biopsy and intratumoral EBUS-TBNA were used to assess the peripheral and central tumor microenvironment respectively. Results The CD39 + CD8 + T cells were ubiquitously infiltrated in lung cancer tissue, as well as dominantly accumulated in peritumoral compartment of larger tumor. In comparison to their CD39- counterparts, CD39 + CD8 + T cells from both sites showed significantly higher expression of PD-1 in line with co-distribution of PD-1 + CD8 + T cell in TME of lung cancer. Particularly, most of CD39 + CD8 + T cells located at peripheral TME exhibited an exhausted phenotype compatible with PD-1 expression in contrast to the reported center of tumor. Furthermore, compared with CD39 + CD8 + T cells, PD-1 + CD39 + CD8 + T cells act as a better biomarker to predict response to anti-PD-1 therapy. Conclusion Spatial heterogeneity may be critical to elicit CD39 expression on lung cancer associated CD8 + T cells. More increased of PD-1 + CD39 + CD8 + T cells within peripheral TME constitute tumorigenic role and act as a candidate biomarker for immunotherapy to lung cancer.

show abstract

“…Notably, they are the most commonly encountered immune infiltrating cells within the tumor microenvironment. Of particular concern in CCA is the presence of high levels of M2 macrophages, which have been shown to be strongly associated with carcinogenesis and poor outcomes in with CCA, as evidenced by prior studies (42)(43)(44). TAMs, a subtype of M2 macrophages, exert potent pro-tumor effects.…”

Section: Innate Immune Cellsmentioning

confidence: 99%

Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)

Yang,

Zou,

Dai

et al. 2023

Int J Oncol

View full text Add to dashboard Cite

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy originating from the epithelial system of the bile ducts, and its incidence in recent years is steadily increasing. The immune microenvironment of CCA is characterized by diversity and complexity, with a substantial presence of cancer-associated fibroblasts and immune cell infiltration, which plays a key role in regulating the distinctive biological behavior of cholangiocarcinoma, including tumor growth, angiogenesis, lymphangiogenesis, invasion and metastasis. Despite the notable success of immunotherapy in the treatment of solid tumors in recent years, patients with CCA have responded poorly to immune checkpoint inhibitor therapy. The interaction of tumor cells with cellular components of the immune microenvironment can regulate the activity and function of immune cells and form an immunosuppressive microenvironment, which may cause ineffective immunotherapy. Therefore, the components of the tumor immune microenvironment appear to be novel targets for immune therapies. Combination therapy focusing on immune checkpoint inhibitors is a promising and valuable first-line or translational treatment approach for intractable biliary tract malignancies. The present review discusses the compositional characteristics and regulatory factors of the CCA immune microenvironment and the possible immune escape mechanisms. In addition, a summary of the advances in immunotherapy for CCA is also provided. It is hoped that the present review may function as a valuable reference for the development of novel immunotherapeutic strategies for CCA.

show abstract

Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis

Cited by 4 publications

References 58 publications

Heterogenous distribution of PD-1+CD39+CD8+ T cell in TME defined its immunotherapeutic biomarker in lung cancer

Heterogenous distribution of PD-1+CD39+CD8+ T cell in TME defined its immunotherapeutic biomarker in lung cancer

Spatial distribution of PD-1+CD39+CD8+ T cell in TME refined its tumorigenic and immunotherapeutic biomarker in lung cancer

Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)

Contact Info

Product

Resources

About