High Numbers and Densities of PD1+ T-Follicular Helper Cells in Triple-Negative Breast Cancer Draining Lymph Nodes Are Associated with Lower Survival

Bronsert, Peter; Schoenfeld, Anna von; Hidalgo, José Villacorta; Kraft, Stefan; Pfeiffer, Jens; Erbes, Thalia; Werner, Martin; Seidl, Maximilian

doi:10.3390/ijms21175948

Cited by 3 publications

(4 citation statements)

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“…This study also identifies that TI PD-1 + CD39 + Tconvs express more TOX and its target genes than TI PD-1 -Tconvs (Balanca et al, 2021). In follicular helper T cells (Tfhs), which are responsible for priming B cells to produce neutralizing antibodies (Vinuesa et al, 2016;Crotty, 2019), PD-1 is found to regulate Tfh localization and function in human and mouse tumors (Shi J. et al, 2018;Bronsert et al, 2020;Sanchez-Alonso et al, 2020). Indeed, a high frequency of PD-1 + Tfhs correlates with poor prognosis in breast and colorectal tumors (Gu-Trantien et al, 2013;Shi W. et al, 2018;Bronsert et al, 2020).…”

Section: Expression and Functionmentioning

confidence: 99%

“…In follicular helper T cells (Tfhs), which are responsible for priming B cells to produce neutralizing antibodies (Vinuesa et al, 2016;Crotty, 2019), PD-1 is found to regulate Tfh localization and function in human and mouse tumors (Shi J. et al, 2018;Bronsert et al, 2020;Sanchez-Alonso et al, 2020). Indeed, a high frequency of PD-1 + Tfhs correlates with poor prognosis in breast and colorectal tumors (Gu-Trantien et al, 2013;Shi W. et al, 2018;Bronsert et al, 2020). Intriguingly, Tfhs are also found to directly promote TI CD8 + T cell effector function by secreting IL-21 in colorectal tumors as well as B cell priming (Shi W. et al, 2018).…”

Section: Expression and Functionmentioning

confidence: 99%

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Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy

Kim

2021

Front. Cell Dev. Biol.

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In the tumor immune microenvironment (TIME), tumor cells interact with various cells and operate various strategies to avoid antitumor immune responses. These immune escape strategies often make the TIME resistant to cancer immunotherapy. Neutralizing immune escape strategies is necessary to overcome resistance to cancer immunotherapy. Immune checkpoint receptors (ICRs) expressed in effector immune cells inhibit their effector function via direct interaction with immune checkpoint ligands (ICLs) expressed in tumor cells. Therefore, blocking ICRs or ICLs has been developed as a promising cancer immunotherapy by reinvigorating the function of effector immune cells. Among the ICRs, programmed cell death 1 (PD-1) has mainly been antagonized to enhance the survival of human patients with cancer by restoring the function of tumor-infiltrating (TI) CD8+ T cells. It has been demonstrated that PD-1 is expressed not only in TI CD8+ T cells, but also in other TI immune cells and even tumor cells. While PD-1 suppresses the function of TI CD8+ T cells, it is controversial whether PD-1 suppresses or amplifies the suppressive function of TI-suppressive immune cells (e.g., regulatory T cells, tumor-associated macrophages, and myeloid cells). There is also controversy regarding the role of tumor-expressing PD-1. Therefore, a precise understanding of the expression pattern and function of PD-1 in each cell subset is important for improving the efficacy of cancer immunotherapy. Here, we review the differential role of PD-1 expressed by various TI immune cells and tumor cells. We focused on how cell-type-specific ablation or blockade of PD-1 affects tumor growth in a murine tumor model. Furthermore, we will also describe how the blockade of PD-1 acts on TI immune cells in human patients with cancer.

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Section: Expression and Functionmentioning

confidence: 99%

Section: Expression and Functionmentioning

confidence: 99%

Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy

Kim

2021

Front. Cell Dev. Biol.

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“…Consistently, it has been reported that a higher infiltration of intra-tumoral PD1-positive cells was significantly associated with shorter OS and disease-free survival of BCAs [ 17 , 18 ]. A higher number of PD1-positive T-follicular helper T cells in sentinel lymph nodes were also associated with shorter survival of triple-negative BCAs [ 33 ]. Higher expression of PD1 mRNA in peripheral blood was associated with shorter OS, but, in contrast, higher PD1 mRNA in tumor tissue was associated with favorable OS in BCAs [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients

Choi,

Ahn,

Zhang

et al. 2023

Diagnostics

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Background: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. Methods: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. Results: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. Conclusions: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

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“…Numerous studies have demonstrated that the infiltration of follicular helper T cells in multiple malignancies is positively associated with survival, including that of non-small-cell lung cancer [ 36 ], colorectal cancer [ 37 ], and breast cancer [ 38 ]. Furthermore, Bronsert et al reported that high numbers and densities of PD1+ follicular helper T cells were linked to adverse prognosis in triple-negative breast cancer [ 39 ]. Taken together, we speculated that the MALAT1/miR-1271-5p/KIAA1324 axis is closely related to the poor prognosis of ccRCC by regulating follicular helper T cell infiltration.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Prognostic Signatures for Clear Cell Renal Cell Carcinoma Based on ceRNA Network Construction and Immune Infiltration Analysis

Zhou

Wen

et al. 2022

Disease Markers

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Objective. Clear cell renal cell carcinoma (ccRCC) carries significant morbidity and mortality globally and is often resistant to conventional radiotherapy and chemotherapy. Immune checkpoint blockade (ICB) has received attention in ccRCC patients as a promising anticancer treatment. Furthermore, competitive endogenous RNA (ceRNA) networks are crucial for the occurrence and progression of various tumors. This study was aimed at identifying reliable prognostic signatures and exploring potential mechanisms between ceRNA regulation and immune cell infiltration in ccRCC patients. Methods and Results. Gene expression profiling and clinical information of ccRCC samples were obtained from The Cancer Genome Atlas (TCGA) database. Through comprehensive bioinformatic analyses, differentially expressed mRNAs (DEmRNAs; n = 131 ), lncRNAs (DElncRNAs; n = 12 ), and miRNAs (DEmiRNAs; n = 25 ) were identified to establish ceRNA networks. The CIBERSORT algorithm was applied to calculate the proportion of 22 types of tumor-infiltrating immune cells (TIICs) in ccRCC tissues. Subsequently, univariate Cox, Lasso, and multivariate Cox regression analyses were employed to construct ceRNA-related and TIIC-related prognostic signatures. In addition, we explored the relationship between the crucial genes and TIICs via coexpression analysis, which revealed that the interactions between MALAT1, miR-1271-5p, KIAA1324, and follicular helper T cells might be closely correlated with the progression of ccRCC. Ultimately, we preliminarily validated that the potential MALAT1/miR-1271-5p/KIAA1324 axis was consistent with the ceRNA theory by qRT-PCR in the ccRCC cell lines. Conclusion. On the basis of the ceRNA networks and TIICs, we constructed two prognostic signatures with excellent predictive value and explored possible molecular regulatory mechanisms, which might contribute to the improvement of prognosis and individualized treatment for ccRCC patients.

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High Numbers and Densities of PD1+ T-Follicular Helper Cells in Triple-Negative Breast Cancer Draining Lymph Nodes Are Associated with Lower Survival

Cited by 3 publications

References 29 publications

Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy

Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy

FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients

Identification of Novel Prognostic Signatures for Clear Cell Renal Cell Carcinoma Based on ceRNA Network Construction and Immune Infiltration Analysis

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