scholarly journals Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells

Cell Reports ◽  
2021 ◽  
Vol 37 (7) ◽  
pp. 110013
Author(s):  
Elisa Matas-Rico ◽  
Elselien Frijlink ◽  
Irene van der Haar Àvila ◽  
Apostolos Menegakis ◽  
Maaike van Zon ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Tumor Infiltration

Ectopic Tcf1 expression instills a stem-like program in exhausted CD8+ T cells to enhance viral and tumor immunity

2020 ◽  
Author(s):  
Qiang Shan ◽  
Sheng’en Hu ◽  
Xia Chen ◽  
Derek B. Danahy ◽  
Vladimir P. Badovinac ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Cd8 T Cells

scholarly journals 540 Baseline mTOR transcriptional signatures in CD8 T cells are associated with immune-related adverse events but not anti-tumor responses in patients receiving immune checkpoint inhibitors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A570-A570
Author(s):  
Chen Zhao ◽  
Matthew Mule ◽  
Andrew Martins ◽  
Iago Pinal Fernandez ◽  
Renee Donahue ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Events ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Effector Memory ◽  
Link Type ◽  
Anti Tumor Activity

BackgroundImmune checkpoint inhibitors (ICIs) have changed the cancer treatment landscape, but immune-related adverse events (irAEs) can affect a wide range of tissues in patients receiving ICIs. Severe irAEs can be life-threatening or fatal and prohibit patients from receiving further ICI treatment. While the clinical features of irAEs are well documented, the pathological mechanisms and predictive biomarkers are largely unknown. In addition, there is a critical need to preserve ICI-induced anti-tumor immunity while controlling for irAEs, which requires deciphering molecular and cellular signatures associated specifically with irAEs beyond those more generally linked to anti-tumor immunity.MethodsTo unbiasedly identify immune cells and states associated with irAEs, we applied CITE-seq to measure transcripts and surface proteins (83 protein markers) from PBMCs collected from patients with thymic epithelial tumors before and after treatment with an anti-PD-L1 antibody (avelumab, NCT01772004, NCT03076554).ResultsSamples from 9 patients were analyzed. No patient had a history of pre-existing paraneoplastic autoimmune disease. Anti-tumor activity was observed in all cases, and 5 patients had clinical and/or biochemical evidence of immune-related muscle inflammation (myositis with or without myocarditis). Multilevel models applied within highly resolved cell clusters revealed transcriptional states associated with ICI response and more uniquely with irAEs. A total of 190,000 cells were included in the analysis after quality control. Most notably, CD45RA+ effector memory CD8 T cells with an mTOR transcriptional signature were highly enriched at baseline and post treatment in patients with irAEs.ConclusionsOur findings suggest the potential therapeutic avenues by using mTOR inhibitors to dampen autoimmune responses while potentially sparing anti-tumor activity, to prevent treatment discontinuation and improve clinical outcomes for cancer patients treated with ICIs.AcknowledgementsThis research was supported in part by the Intramural Research Program of the NCI (the Center for Cancer Research), NIAID and NIAMS, and through a Cooperative Research and Development Agreement between the National Cancer Institute and EMD Serono.Trial RegistrationNCT01772004, NCT03076554Ethics ApprovalThis study is approved by NCI institutional review board.

scholarly journals Immunostimulation During and After R-CHOP Therapy for B-Cell Lymphoma

2016 ◽  
Vol 01 (01) ◽  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treg Cells ◽  
T Cell Subsets ◽  
T Helper ◽  
Chop Therapy

Backgrounds: Many studies show an immune imbalance in the tumor environment; some reports show that the T helper 1 (Th1)/ T helper 2 (Th2) ratio, the number of regulatory T-cells (Treg cells) or CD8+T-cells, and the CD8+Tcell/Treg cell ratio are associated with tumor suppression and expansion. Additionally, chemotherapy was reported to affect the immunity of patients with malignancy. Patients and Methods: Using flow cytometry we measured peripheral blood lymphocytes including non T-cells, as well as T-cell subsets such as CD3+T-cells, CD4+T-cells, CD8+T-cells, Treg cells, Th1 cells and Th2 cells before treatment, at the fourth cycle, and at 1, 3, 6 and 12 months after treatment in 21 patients with B-cell lymphoma receiving R-CHOP therapy. We also analyzed the changes in three immune indexes that reflect anti-tumor immunity (the CD4/CD8 ratio, the CD8/Treg ratio and the Th1/Th2 ratio). Results: Compared to pre-treatment there were significant decreases in the CD4/CD8 ratio between 1 month and 12 months after treatment (p<0.001, for all time points). The CD8/Treg ratio gradually increased with treatment with significant increases observed at 6 months (p=0.009) and 12 months after treatment (p=0.002). The Th1/ Th2 ratio showed a significant increase only before 4 cycles of therapy (p=0.007). Conclusion: Based on the changes in these three immune indexes, we propose that anti-tumor immunity improved after R-CHOP therapy, which enhanced the efficacy of R-CHOP therapy for lymphoma as well as its direct cytotoxic activity

scholarly journals 330 Deficiency of Bach2 results in improved tumor immunity by enhancing effector function in CD8 T cells

2017 ◽  
Vol 137 (10) ◽  
pp. S249
Author(s):  
Y. Sato ◽  
M. Matsui-Watanabe ◽  
M. Matsumoto ◽  
D.R. Sharda ◽  
K. Igarashi ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Effector Function

scholarly journals Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells

2005 ◽  
Vol 202 (7) ◽  
pp. 885-891 ◽  
Author(s):  
Kuibeom Ko ◽  
Sayuri Yamazaki ◽  
Kyoko Nakamura ◽  
Tomohisa Nishioka ◽  
Keiji Hirota ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Effector T Cells ◽  
Tumor Rejection ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Ifn Γ ◽  
Advanced Tumors

T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor family–related protein (GITR) can evoke effective tumor immunity. A single administration of agonistic anti-GITR monoclonal antibody (mAb) to tumor-bearing mice intravenously or directly into tumors provoked potent tumor-specific immunity and eradicated established tumors without eliciting overt autoimmune disease. A large number of CD4+ and CD8+ T cells, including interferon (IFN)-γ–secreting cells, infiltrated regressing tumors. Tumor-specific IFN-γ–secreting CD4+ and CD8+ T cells also increased in the spleen. The treatment led to tumor rejection in IFN-γ–intact mice but not IFN-γ–deficient mice. Furthermore, coadministration of anti-GITR and anti–CTLA-4 mAbs had a synergistic effect, leading to eradication of more advanced tumors. In contrast, coadministration of anti-CD25 and anti-GITR mAbs was less effective than anti-GITR treatment alone, because anti-CD25 depleted both CD25+-activated effector T cells and CD25+CD4+ naturally occurring regulatory T (T reg) cells. Importantly, CD4+ T cells expressing the T reg–specific transcription factor Foxp3 predominantly infiltrated growing tumors in control mice, indicating that tumor-infiltrating natural Foxp3+CD25+CD4+ T reg cells may hamper the development of effective tumor immunity. Taken together, T cell stimulation through GITR attenuates T reg–mediated suppression or enhances tumor-killing by CD4+ and CD8+ effector T cells, including those secreting IFN-γ, or both. Agonistic anti-GITR mAb is therefore instrumental in treating advanced cancers.

scholarly journals Regulatory B1a Cells Suppress Melanoma Tumor Immunity via IL-10 Production and Inhibiting T Helper Type 1 Cytokine Production in Tumor-Infiltrating CD8+ T Cells

2019 ◽  
Vol 139 (7) ◽  
pp. 1535-1544.e1 ◽  
Author(s):  
Tadahiro Kobayashi ◽  
Kyosuke Oishi ◽  
Ai Okamura ◽  
Shintaro Maeda ◽  
Akito Komuro ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Cytokine Production ◽  
T Helper ◽  
Melanoma Tumor ◽  
B1a Cells ◽  
Type 1 Cytokine ◽  
Helper Type
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