The Roles of CCR7 for the Homing of Memory CD8+ T Cells into Their Survival Niches

Choi, Hanbyeul; Song, Heonju; Jung, Yong Woo

doi:10.4110/in.2020.20.e20

Cited by 38 publications

(27 citation statements)

References 99 publications

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“…Pearson correlation coefficients (R), P values, and estimates of fitted line parameter are shown. (22). The factor or set of factors causing T cells to lose CCR7 following surgical resection requires more in-depth studies of patient cohorts.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome

Otvos

Alban

Grabowski

et al. 2021

Clinical Cancer Research

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Purpose: Glioblastoma (GBM) immunotherapy clinical trials are generally initiated after standard-of-care treatment-including surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment-has either begun or failed. However, the impact of these interventions on the antitumoral immune response is not well studied. While discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated into clinical trial design, the impact of surgical resection and steroids on the antitumor immune response has yet to be determined.Experimental Design: We developed a murine model integrating tumor resection and steroid treatment and used flow cytometry to analyze systemic and local immune changes. These mouse model findings were validated in a cohort of 95 patients with primary GBM.Results: Using our murine resection model, we observed a systemic reduction in lymphocytes corresponding to increased tumor volume and decreased circulating lymphocytes that was masked by dexamethasone treatment. The reduction in circulating T cells was due to reduced CCR7 expression, resulting in T-cell sequestration in lymphoid organs and the bone marrow. We confirmed these findings in a cohort of patients with primary GBM and found that prior to steroid treatment, circulating lymphocytes inversely correlated with tumor volume. Finally, we demonstrated that peripheral lymphocyte content varies with progression-free survival and overall survival, independent of tumor volume, steroid use, or molecular profiles.Conclusions: These data reveal that prior to intervention, increased tumor volume corresponds with reduced systemic immune function and that peripheral lymphocyte counts are prognostic when steroid treatment is taken into account.

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Section: Discussionmentioning

confidence: 99%

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome

Otvos

Alban

Grabowski

et al. 2021

Clinical Cancer Research

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“…Hence, they can be activated in the lymph nodes and spleen and developed into effector T cells. Effector T cells can move to infected or tumorigenic locus by the downregulation of CCR7 expression ( Choi et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change

Tian

Feng

Wang

et al. 2021

Front. Mol. Biosci.

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The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 (CCR7) was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of CCR7 and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high CCR7 expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low CCR7 expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression, suggesting that CCR7 might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of CCR7 might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.

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“…CCR7 regulates the homing of T cells to lymphoid organs. Controlling the migration of memory T cells by CCR7 modulation may determine their destiny by changing the location ( 12 ). In addition to controlling cell migration, CCR7‐mediated signals affect T‐cell homeostasis in lymph nodes and also influence T‐cell activation and polarization ( 13 ).…”

Section: Phenotypic Molecules Of T Cell Differentiationmentioning

confidence: 99%

“…Depending on the subtypes or functions of memory T cells, CCR7 may also determine the niche suitable for their survival. So CCR7 plays a crucial role in the activation of naïve T cells (Tn) as well as the development and maintenance of memory T cell subsets ( 12 ).…”

Section: Phenotypic Molecules Of T Cell Differentiationmentioning

confidence: 99%

“…The phenotype is a both effective and efficient indicator to analyze differentiation status of T cells. Quite a few clinical trials have shown that infused T-cell differentiation phenotypes are significantly relevant to clinical outcomes in anti-cancer therapies (5)(6)(7)(8)(9)(10)(11). However, the specific differentiation phenotypes indicating the strongest T-cell therapeutic effects are still controversial.…”

Section: Introductionmentioning

confidence: 99%

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A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy

2021

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T-cell therapy, usually with ex-vivo expansion, is very promising to treat cancer. Differentiation status of infused T cells is a crucial parameter for their persistence and antitumor immunity. Key phenotypic molecules are effective and efficient to analyze differentiation status. Differentiation status is crucial for T cell exhaustion, in-vivo lifespan, antitumor immunity, and even antitumor pharmacological interventions. Strategies including cytokines, Akt, Wnt and Notch signaling, epigenetics, and metabolites have been developed to produce less differentiated T cells. Clinical trials have shown better clinical outcomes from infusion of T cells with less differentiated phenotypes. CD27+, CCR7+ and CD62L+ have been the most clinically relevant phenotypic molecules, while Tscm and Tcm the most clinically relevant subtypes. Currently, CD27+, CD62L+ and CCR7+ are recommended in the differentiation phenotype to evaluate strategies of enhancing stemness. Future studies may discover highly clinically relevant differentiation phenotypes for specific T-cell production methods or specific subtypes of cancer patients, with the advantages of precision medicine.

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The Roles of CCR7 for the Homing of Memory CD8+ T Cells into Their Survival Niches

Cited by 38 publications

References 99 publications

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome

CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change

A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy

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