CD103+CD8+ tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer

Jin, Kaifeng; Yu, Yanfang; Zeng, Han; Liu, Zhaopei; You, Runze; Zhang, Hongyi; Liu, Chunnan; Su, Xiaohe; Yan, Sen; Chang, Yuan; Xu, Liang; Xu, Jiejie; Zhu, Yu

doi:10.1038/s41416-022-01725-6

Cited by 23 publications

(18 citation statements)

References 36 publications

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“…While these reports do indicate that some CD8 + CD103 + Treg may have both suppressive and cytolytic potential, the current the literature is still unable to phenotypically distinguish between the immunosuppressive, cytolytic and dual function populations. A possible explanation to these varying mechanisms used by CD8 + CD103 + Treg is that CD103 expression is likely not a conserved marker of CD8 + Treg, as several studies have also reported CD103 expression as a marker of activated tissue-resident memory T-cells (Trm) ( 196 , 197 ). In fact, CD8 + CD103 + Trm cells have been shown to be significant contributors to anti-tumor immunity due to their substantial cytotoxicity and cytokine production potential ( 196 – 199 ).…”

Section: The Role Of Cd8 + Treg In Immunosuppressi...mentioning

confidence: 99%

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

et al. 2022

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Regulatory T-cells (Treg) are critical for the maintenance of immune homeostasis and tolerance induction. While the immunosuppressive mechanisms of Treg have been extensively investigated for decades, the mechanisms responsible for Treg cytotoxicity and their therapeutic potential in regulating immune responses have been incompletely explored and exploited. Conventional cytotoxic T effector cells (Teffs) are known to be important for adaptive immune responses, particularly in the settings of viral infections and cancer. CD4+ and CD8+ Treg subsets may also share similar cytotoxic properties with conventional Teffs. Cytotoxic effector Treg (cyTreg) are a heterogeneous population in the periphery that retain the capacity to suppress T-cell proliferation and activation, induce cellular apoptosis, and migrate to tissues to ensure immune homeostasis. The latter can occur through several cytolytic mechanisms, including the Granzyme/Perforin and Fas/FasL signaling pathways. This review focuses on the current knowledge and recent advances in our understanding of cyTreg and their potential application in the treatment of human disease, particularly Graft-versus-Host Disease (GVHD).

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Section: The Role Of Cd8 + Treg In Immunosuppressi...mentioning

confidence: 99%

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

et al. 2022

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“…In addition, stromal lymphocytic in ltrate (SLI) was shown to be a reliable marker of poor BLCA patient prognosis and positively correlated with histological grade, tumor stage, and lymph node status (Furuya et al, 2019). The presence of CD163 + and CD103 + macrophages also predicted the poor prognosis of patients with primary T1 high-grade bladder urothelial carcinoma (Yang et al, 2019;Jin et al, 2022). However, the predictors identi ed to date remain insu cient for reliable BLCA prognosis and precision treatment.…”

Section: Discussionmentioning

confidence: 99%

Using Necroptosis-Associated Genes To Predict The Immune Microenvironment And Prognosis Of Bladder Urothelial Carcinoma

Liu

Yang

et al. 2022

Preprint

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PURPOSE Bladder urothelial carcinoma (BLCA), the most common urinary tract malignancy, has a high recurrence rate and poor survival at late stages. Necroptosis, a form of programmed cell death, is involved in cancer development and progression, but its function in BLCA prognosis remains unclear. This study sought to investigate the role of necroptosis in the development and prognosis of BLCA. METHODS Clinical information and RNA expression matrix data were obtained from the databases. Survival analysis was performed to obtain survival- and necroptosis-related genes and identify any that overlapped. Consensus clustering analysis was used to create different subgroups by combining the overlapping gene expression matrix and clinical information. The tumor immune microenvironment and immune status of the different subgroups were determined using ESTIMATE, MCPcounter, and ssGSEA analysis. We performed differential analysis on the gene expression matrix of molecular subpopulations to find and screen out differentially expressed genes (DEGs). GO, KEGG, GSVA, and GSEA analyses were used to elucidate the underlying mechanisms of the DEGs. Lasso Cox regression analysis was used to build a prognostic risk model and perform a pan-cancer analysis of the screened genes. The results were used to define potential roles for these genes in other cancers and assess the efficacy of the risk model. RESULTS Cluster analysis identified two subgroups, C1 and C2, with significantly different survival rates. ESTIMATE, MCPcounter, and ssGSEA analyses showed that high immune scores, tumor purity, and immune status were associated with poorer prognoses. GO and KEGG functional enrichment analyses indicated that DEGs were mainly focused on tumor proliferation, invasion, and immunity and GSEA analysis suggested that necroptosis may affect Toll-like receptor signaling pathways, MAPK cascade regulation of leukocyte trafficking, and cytokine-cytokine receptor interaction pathways. Lasso Cox regression analysis was used to model the prognostic risk while screening for representative necroptosis-associated genes, ANXA1, ATAD3A, and TRPC6, with high potential for survival prediction in BLCA patients. The pan-cancer analysis indicated that the three representative genes were also differentially expressed in other cancer types. CONCLUSION Expression of necroptosis-related genes such as ANXA1, ATAD3A, and TRPC6 correlate with the immune microenvironment of BLCA patients and have the potential for use in disease prognostics.

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“…CD8+ TRM cells were initially defined in infected tissues such as the skin, lung, and intestine ( Gebhardt et al, 2009 ; Masopust et al, 2010 ; Purwar et al, 2011 ). Gradually, CD8+ TRM cells were found in TME and were associated with the prognosis of tumor patients ( Edwards et al, 2018 ; Savas et al, 2018 ; Abdeljaoued et al, 2022 ; Anadon et al, 2022 ; Jin et al, 2022 ; Smith, 2022 ). Different phenotypes are expressed by CD8+ TRM cells to destroy tumor cells effectively.…”

Section: Effector Phasementioning

confidence: 99%

“…For instance, CD103 is essential in the skin, lung, and intestine ( Gebhardt et al, 2009 ; Ganesan et al, 2017 ; Dumauthioz et al, 2018 ), but it is dispensable for the liver ( Ghilas et al, 2020 ). CD103+ CD8+ TRM cells were associated with improved survival in cancer patients ( Edwards et al, 2018 ; Savas et al, 2018 ; Hewavisenti et al, 2020 ; Shen et al, 2021 ; Huang et al, 2022b ; Jin et al, 2022 ). For example, CD103+ CD8+ TRM cells infiltrating into TME were associated with a better adjuvant therapeutic benefit and were considered as an ideal prognostic biomarker in muscle-invasive bladder cancer.…”

Section: Effector Phasementioning

confidence: 99%

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Wang

Zhuling³

et al. 2022

Front. Genet.

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In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

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CD103+CD8+ tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer

Cited by 23 publications

References 36 publications

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

Using Necroptosis-Associated Genes To Predict The Immune Microenvironment And Prognosis Of Bladder Urothelial Carcinoma

The soldiers needed to be awakened: Tumor-infiltrating immune cells

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