CXCR5+ CD8+ T cells potently infiltrate pancreatic tumors and present high functionality

Bai, Minghui; Zheng, Yu; Liu, Haichao; Su, Baowei; Yang, Zhan; He, Hua

doi:10.1016/j.yexcr.2017.09.039

Cited by 61 publications

(43 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tfc cells have been studied in the blood and LN of SIV+ primate models (45, 46), the LNs of LCMV mouse models (33), as well as the blood, tumors, and LN of adult humans (32, 33, 47–49). Multiple groups reported Tfc cells have similar B cell follicle homing abilities to Tfh cells, and the potential to control viral infection by eliminating infected T cells and B cells in the follicle.…”

Section: Discussionmentioning

confidence: 99%

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease

McCarty

Mwamzuka²,

Marshed³

et al. 2018

Front. Immunol.

View full text Add to dashboard Cite

BackgroundT follicular helper (Tfh) cells are crucial for B cell differentiation and antigen-specific antibody production. Dysregulation of Tfh-mediated B cell help weakens B cell responses in HIV infection. Moreover, Tfh cells in the lymph node and peripheral blood comprise a significant portion of the latent HIV reservoir. There is limited data on the effects of perinatal HIV infection on Tfh cells in children. We examined peripheral Tfh (pTfh) cell frequencies and phenotype in HIV-infected children and their associations with disease progression, immune activation, and B cell differentiation.MethodsIn a Kenyan cohort of 76 perinatally HIV-infected children, comprised of 43 treatment-naïve (ART−) and 33 on antiretroviral therapy (ART+), and 42 healthy controls (HIV−), we identified memory pTfh cells, T cell activation markers, and B cell differentiation states using multi-parameter flow cytometry. Soluble CD163 and intestinal fatty acid-binding protein plasma levels were quantified by ELISA.ResultsART− children had reduced levels of pTfh cells compared with HIV− children that increased with antiretroviral therapy. HIV+ children had higher programmed cell death protein 1 (PD-1) expression on pTfh cells, regardless of treatment status. Low memory pTfh cells with elevated PD-1 levels correlated with advancing HIV disease status, indicated by increasing HIV viral loads and T cell and monocyte activation, and decreasing %CD4 and CD4:CD8 ratios. Antiretroviral treatment, particularly when started at younger ages, restored pTfh cell frequency and eliminated correlations with disease progression, but failed to lower PD-1 levels on pTfh cells and their associations with CD4 T cell percentages and activation. Altered B cell subsets, with decreased naïve and resting memory B cells and increased activated and tissue-like memory B cells in HIV+ children, correlated with low memory pTfh cell frequencies. Last, HIV+ children had decreased proportions of CXCR5+ CD8 T cells that associated with low %CD4 and CD4:CD8 ratios.ConclusionLow memory pTfh cell frequencies with high PD-1 expression in HIV+ children correlate with worsening disease status and an activated and differentiated B cell profile. This perturbed memory pTfh cell population may contribute to weak vaccine and HIV-specific antibody responses in HIV+ children. Restoring Tfh cell capacity may be important for novel pediatric HIV cure and vaccine strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease

McCarty

Mwamzuka²,

Marshed³

et al. 2018

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…After PD-1 blockade, CXCR5 + populations are capable of expanding and differentiating into CXCR5cells to mediate tumor control (28). Importantly, CXCR5 + CD8 + T cells with high functionality have been found in both circulation and tumor microenvironment on human pancreatic cancer and lung cancer (29,30). Third, host PD-L1 expression is crucial for PD-1 therapy.…”

Section: Introductionmentioning

confidence: 99%

2B4 but not PD-1 blockade improves mortality in septic animals with preexisting malignancy

Chen¹,

Xue²,

Zhang³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

“…18 In HBV-related liver cancer, CXCR5 + CD8 + T cells are likely to be initially induced by viral responses, and then act on tumor cells. 19 As it is demonstrated in previous studies, CXCR5 + CD8 + T cell frequency is positively correlated with the overall survival of patients with various malignancies, including the malignancies mentioned above along with colorectal, 20 pancreas, 21 lung 22 and thyroid 23 cancer. Intriguingly, a study revealed that CXCR5 + CD8 + T cells provide a proliferation burst after PD-1 blockade in LCMV infection, suggesting its sensitivity to anti-PD-1 therapy.…”

Section: Introductionmentioning

confidence: 56%

“…Intriguingly, we found CXCR5 + CD8 + T cells could serve as a more powerful prognosticator than CD8 + T cells in MIBC, which was in line with its impressive anti-tumor function as discovered in other tumor types. [18][19][20][21][22][23] We have previously reported several immune cells infiltration associated with ACT benefit in MIBC, such as tumor-infiltrating neutrophils, mast cells, B cells, and IL-22 + cell. 25,[31][32][33][34] Remarkably, we revealed the outstanding predictive ability of CXCR5 + CD8 + T cells in response to ACT in MIBC.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5 ⁺ CD8 ⁺ T cell abundance

et al. 2020

View full text Add to dashboard Cite

show abstract

CXCR5+ CD8+ T cells potently infiltrate pancreatic tumors and present high functionality

Cited by 61 publications

References 25 publications

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease

2B4 but not PD-1 blockade improves mortality in septic animals with preexisting malignancy

Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5 ⁺ CD8 ⁺ T cell abundance

Contact Info

Product

Resources

About

CXCR5+ CD8+ T cells potently infiltrate pancreatic tumors and present high functionality

Cited by 61 publications

References 25 publications

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease

Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease

2B4 but not PD-1 blockade improves mortality in septic animals with preexisting malignancy

Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5 + CD8 + T cell abundance

Contact Info

Product

Resources

About

Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5 ⁺ CD8 ⁺ T cell abundance