CXCR5+CD8+ T cells present elevated capacity in mediating cytotoxicity toward autologous tumor cells through interleukin 10 in diffuse large B-cell lymphoma

Tang, Jiahong; Zha, Jun; Guo, Xutao; Shi, Pengcheng; Xu, Bing

doi:10.1016/j.intimp.2017.06.020

Cited by 21 publications

(18 citation statements)

References 28 publications

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“…Cancer represents a situation of chronic, low-level self-antigen much like the situation induced by chronic viral infection. In B cell lymphoma-bearing mice and diffuse large B cell lymphoma patients, CXCR5+ CD8 T cells likely arise to directly target cancer cells (13, 23). Whereas, in HBV-related hepatocellular carcinoma, viral responses may initially induce CXCR5+ CD8 T cells that then target cancer cells (16).…”

Section: Cxcr5+ Cd8 T Cell Functionmentioning

confidence: 99%

“…In spite of the fairly robust cytolytic potential and activity by CXCR5+ CD8 T cells, tumor cells likely employ inhibitory mechanisms to suppress CXCR5+ CD8 T cell function. In vitro neutralization of IL-10 or IL-10R pathway improved granzyme A, granzyme B, and perforin-mediated cytotoxicity by CXCR5+ CD8 T cells (23). IL-10 or PD-1L blockade induced CXCR5+ CD8 T cell targeted specific cell lysis of autologous tumor cells (16).…”

Section: Cxcr5+ Cd8 T Cell Functionmentioning

confidence: 99%

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CXCR5+ CD8 T Cells: Protective or Pathogenic?

Valentine

Hoyer

2019

Front. Immunol.

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CD8 T cells are infrequently considered part of germinal center reactions. Yet, a distinct CXCR5+ CD8 T cell subset identified within the B cell follicle and germinal center in situations of chronic antigen has recently been defined. CXCR5+ CD8 T cells maintain transcriptional and phenotypic features consistent with the CD8 T cell nomenclature of a non-exhausted, effector memory population. CD8 T cell localization to the B cell follicle suggests a functional profile similar to CD4 T follicular helper cells that are licensed to promote B cell responses. The functional mechanisms defined under different immune settings, while largely similar, differentially control disease pathogenesis. CXCR5+ CD8 T cells control viral load during infection, and also promote antibody-mediated autoimmune disease progression. The existence of this novel CXCR5+ CD8 T cell subset in human and murine models of disease may provide a paradigm shift in our understanding of germinal center reactions.

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Section: Cxcr5+ Cd8 T Cell Functionmentioning

confidence: 99%

Section: Cxcr5+ Cd8 T Cell Functionmentioning

confidence: 99%

CXCR5+ CD8 T Cells: Protective or Pathogenic?

Valentine

Hoyer

2019

Front. Immunol.

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“…GC-resident or CXCR5 pos CD8 + T cells are present in lymphoid tissues of humans ( 20 , 83 – 85 ) and macaques ( 19 , 31 ). In fact, three decades ago, high frequencies of CD8 + T cells were found in inflamed lymphoid follicles in heroin addicts and HIV-related lymphadenopathy ( 83 , 84 ).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies suggest that CXCR5 + CD8 + T cells represent a subset of follicular cytotoxic CD8 + T cells and may contribute to virus control in B cell follicles ( 23 ). Indeed, follicular cytotoxic CD8 + T cells express granzyme A and B and perforin at higher levels than their CXCR5 neg counterpart ( 85 ). Interestingly, a study identified a subset of CD8 + T cells with the suppressive activity on T FH cells in rhesus macaques’ LNs and humans’ tonsils ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

T Cell Subsets in the Germinal Center: Lessons from the Macaque Model

Vaccari

Franchini

2018

Front. Immunol.

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Germinal centers (GCs) are organized lymphoid tissue microstructures where B cells proliferate and differentiate into memory B cells and plasma cells. A few distinctive subsets of highly specialized T cells gain access to the GCs by expressing the B cell zone–homing C-X-C chemokine receptor type 5 (CXCR5) while losing the T cell zone–homing chemokine receptor CCR7. Help from T cells is critical to induce B cell proliferation and somatic hyper mutation and to limit GC reactions. CD4+ T follicular helper (TFH) cells required for the formation of GCs and for the generation of long-lived, high-affinity B cells. Regulatory CD4+ (TFR) and CD8+ T cells co-localize with TFH cells and keep their expansion in check, thus limiting GC reactions. A cytotoxic CXCR5pos CD8+ T cell subset has been described in GCs in humans: although low in number, GC CD8+ T cells can expand rapidly during certain viral infections. Because these subsets find their home in secondary lymphoid tissues (lymph nodes and spleen) that are difficult to obtain in humans, GC–homing T cells have been extensively studied in mice. Nevertheless, significant limitations in using this model, such as evolutionary divergences between mice and humans and the lack of an optimal mouse model for certain human diseases, have prompted investigators to characterize GC–homing T cells in macaques instead. This review will focus on discoveries made in macaques, particularly in the non-human primate models of simian immunodeficiency virus and simian–human immunodeficiency virus infection. Indeed, experimental studies in these models have allowed researchers to gain insight into the relative role of follicular T cell subsets in HIV progression, virus persistence, and specific B cell responses induced by HIV vaccines. These discoveries have prompted the testing of novel approaches aimed to manipulate follicular T cells to increase the efficacy of HIV vaccines and to eliminate HIV reservoirs.

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“…Finally, CD160 + CD8 T cells have been shown to express higher PD-1 levels than the CD160 − counterpart, to have less proliferative and cytotoxic potential and to be enriched among CD8 TILs in pancreatic cancer patients ( 69 ). Recently, a CXCR5 + CD8 T cell population has been observed to expand in diffuse large B cell lymphoma ( 232 ), follicular lymphoma ( 144 ) and HBV-related hepatocellular carcinoma ( 137 , 139 , 141 , 149 ). Circulating, tumor infiltrating, and lymphoid CXCR5 + CD8 T cells were shown to co-express PD-1 and, in contrast with chronic viral infection ( 129 , 131 , 134 , 148 ), TIM-3 ( 134 , 140 ), however they were functionally less exhausted than the CXCR5 − CD8 T cell population and expressed genes related to stem-like plasticity and cytotoxicity ( 140 , 141 , 149 ).…”

Section: Hallmarks Of T Cell Exhaustion In Cancermentioning

confidence: 99%

Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure

et al. 2020

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The main role of the human immune system is to eliminate cells presenting foreign antigens and abnormal patterns, while maintaining self-tolerance. However, when facing highly variable pathogens or antigens very similar to self-antigens, this system can fail in completely eliminating the anomalies, leading to the establishment of chronic pathologies. Prototypical examples of immune system defeat are cancer and Human Immunodeficiency Virus-1 (HIV-1) infection. In both conditions, the immune system is persistently exposed to antigens leading to systemic inflammation, lack of generation of long-term memory and exhaustion of effector cells. This triggers a negative feedback loop where effector cells are unable to resolve the pathology and cannot be replaced due to the lack of a pool of undifferentiated, self-renewing memory T cells. In addition, in an attempt to reduce tissue damage due to chronic inflammation, antigen presenting cells and myeloid components of the immune system activate systemic regulatory and tolerogenic programs. Beside these homologies shared between cancer and HIV-1 infection, the immune system can be shaped differently depending on the type and distribution of the eliciting antigens with ultimate consequences at the phenotypic and functional level of immune exhaustion. T cell differentiation, functionality, cytotoxic potential and proliferation reserve, immune-cell polarization, upregulation of negative regulators (immune checkpoint molecules) are indeed directly linked to the quantitative and qualitative differences in priming and recalling conditions. Better understanding of distinct mechanisms and functional consequences underlying disease-specific immune cell dysfunction will contribute to further improve and personalize immunotherapy. In the present review, we describe relevant players of immune cell exhaustion in cancer and HIV-1 infection, and enumerate the best-defined hallmarks of T cell dysfunction. Moreover, we highlight shared and divergent aspects of T cell exhaustion and T cell activation to the best of current knowledge.

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CXCR5+CD8+ T cells present elevated capacity in mediating cytotoxicity toward autologous tumor cells through interleukin 10 in diffuse large B-cell lymphoma

Cited by 21 publications

References 28 publications

CXCR5+ CD8 T Cells: Protective or Pathogenic?

CXCR5+ CD8 T Cells: Protective or Pathogenic?

T Cell Subsets in the Germinal Center: Lessons from the Macaque Model

Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure

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