scholarly journals Dihydroartemisinin broke immune evasion through YAP1/JAK1/STAT1, 3 pathways to enhance anti-PD-1 therapy in hepatocellular carcinoma

2021 ◽  
Author(s):  
Qing Peng ◽  
Shenghao Li ◽  
Xinli Shi ◽  
Yinglin Guo ◽  
Liyuan Hao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Immune Evasion ◽  
Cd8 T Cells ◽  
Liver Tumor ◽  
Therapeutic Strategy ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Tumor Tissues

The efficacy of anti-PD-1 therapy is not as expected in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) was overexpressed and activated in HCC. This study aimed to investigate the potential mechanism and inhibitor of YAP1 on immune evasion, and promote anti-PD-1 therapy in HCC. Here, we showed that dihydroartemisinin (DHA), an FDA approved drug, directly suppressed YAP1 expression, leading to break immune evasion in liver tumor niche, characterized by decreased PD-L1 in liver tumor cells and increased CD8+ T cell infiltration. Mechanismly, YAP1 is not only directly related to PD-L1, but also involved in activating the JAK1/STAT1, 3 pathways. Moreover, Yap1 knockout elevated CD4+ and CD8+ T cells in liver tumor niche of Yap1LKO mice. Consistently, verteporfin, YAP1 inhibitor, decreased TGF-β in liver tumor niche and exhausted CD8+ T cells in spleen. Furthermore, DHA combined with anti-PD-1 treatment promoted CD4+ T cell infiltration in the spleen and CD8+ T cells in tumor tissues. Thus, we provide a new combined therapeutic strategy for anti-PD-1 with DHA, a potent YAP1 inhibitor, in HCC.

Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3061-3061 ◽  
Author(s):  
Mark Selby ◽  
John Engelhardt ◽  
Li-Sheng Lu ◽  
Michael Quigley ◽  
Changyu Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Cell Infiltration ◽  
Preclinical Models ◽  
Concurrent Treatment ◽  
T Cell Infiltration ◽  
Synergistic Antitumor Activity

3061 Background: Interaction of immune checkpoint molecules PD-1 and CTLA-4 and their respective ligands attenuates antitumor T cell responses. In clinical studies, PD-1 blocking antibody (Ab) nivolumab (BMS-936558) or the CTLA-4 blocking Ab ipilimumab result in durable responses in multiple human malignancies. We describe the evaluation of concurrent treatment with anti-PD-1 and anti-CTLA-4 mAbs in preclinical models. Methods: Antitumor activity of treatment with murine homologs of anti-PD-1 (4H2-mIgG1) and anti-CTLA-4 (9D9-mIgG2b) was evaluated in MC38, a murine colon adenocarcinoma model. The effects of concurrent treatment on T cell infiltration of tumors, tumoral expression of PD-L1 and cytokine levels were explored. The preclinical safety profile of concurrent nivolumab + ipilimumab was assessed in a cynomolgus macaque model. Results: Concurrent treatment of MC38 tumors with 4H2-mIgG1 + 9D9-mIgG2b (10 mg/kg Q3d x 3) results in synergistic antitumor activity whereas efficacy with sequential dosing was similar to either agent alone. With concurrent treatment, dose reductions of one Ab relative to a fixed dose of the other resulted in retention of some antitumor activity. Anti-PD-1 enhanced CD8+ T cell infiltration of MC38 tumors and increased tumor PD-L1 expression. Anti-CTLA-4 treatment increased intratumoral CD8+ T cells and reduced intratumoral T regulatory cells. While concurrent treatment did not result in further increases in T cell infiltration, it increased expression of intratumoral cytokines. Anti-PD-1 resulted in down regulation of cell surface and intracellular levels of PD-1 in CD8+ T cells. In cynomolgus macaques, concurrent nivolumab + ipilimumab resulted in dose-dependent gastrointestinal toxicities (diarrhea; body weight loss) not observed in earlier cynomolgus studies with nivolumab and rarely with ipilimumab. These preclinical observations provided the rationale for a dose escalation trial (NCT01024231) of combined nivolumab + ipilimumab in advanced melanoma. Conclusions: Concurrent treatment with anti-PD-1/anti-CTLA-4 resulted in synergistic antitumor activity in preclinical models and supports the evaluation of the combination in clinical studies.

Immunogenomic classification of gastric cancer based on the tumor microenvironments expression of PD-L1 and CD8+ T-cell infiltration.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16578-e16578
Author(s):  
Yu Chen ◽  
Gang Chen ◽  
Jia-ni Xiong ◽  
Bin Lan ◽  
Xuan Gao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cell Infiltration ◽  
Type I ◽  
T Cell Infiltration ◽  
Genetic Features

e16578 Background: Previous data has shown that a positive response to immunotherapy usually relies on active interactions between tumor cells and immunomodulators inside the tumor microenvironment (TME). The aim of this study was to classify gastric cancer (GC) subsets based on the TME immune status according to the expression of PD-L1 and infiltration of CD8+ T cells. Methods: One hundred and eighty-six tumor tissue from gastric cancer patients with a curative D2 gastrectomy were examined for evaluating PD-L1 and CD8+ T cells status using histopathologic analysis. The molecular characteristics of 289 GC samples in TCGA network were further analyzed to distinguish the genetic features of four immune subtypes depending on the presence of PD-L1/CD8+T cell. Results: GC samples were categorized into four types, type I (CD8+/PD-L1+, 60.3%), II (CD8-/PD-L1-, 11.8%), III (CD8-/PD-L1+, 0%), and IV (CD8+/PD-L1-, 27.9%), basing on PD-L1/CD8 expression. The PD-L1 expressing level was geographically associated with the intensity of CD8+ T cell infiltration which was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.003 and p = 0.006). Distinct patterns of genetic profile were described in four types of GC from TCGA database. Type I and III which PD-L1 were overly expressed had comparatively higher MSI and TMB, with EBV mainly enriched in Type I, whereas CIN was more likely to occur in PD-L1 aberrant types II and IV. SNV analysis illustrated higher gene mutations in oncogenes (PIK3CA and ERBB2), and in DNA damage repair related pathway, such as PRKDC, ATM, and SWI/SNF complexes (e.g. ARID1A) in Type I. However, TP53 mutations tend to enrich in Type II and IV. Similar results were obtained by transcriptome analysis. Conclusions: The genetic features of four immune subtypes proof that PD-L1 and CD8+ T cells status are reasonable immunogenomic classification of gastric cancer. SNV analysis prompts a potential mechanism for effectiveness of immunotherapy in Type I patients. Overall, the results may be useful for the development of clinical treatments for the blockade of immune checkpoints.

scholarly journals DNA Methylation based glioblastoma subclassification is related to tumoral T cell infiltration and patient survival

2020 ◽  
Author(s):  
Joost Dejaegher ◽  
Lien Solie ◽  
Zoé Hunin ◽  
Raf Sciot ◽  
David Capper ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Methylation Pattern ◽  
Response To Therapy ◽  
Cell Infiltration ◽  
Mesenchymal Tumors ◽  
T Cell Infiltration

Abstract Background Histologically classified Glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy and clinical outcome. Methods 450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy. Tumor infiltration of T cells, myeloid cells and PD-1 expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy. Results Forty-two tumors had a mesenchymal, 27 a RTK II, 17 a RTK I and 7 an IDH DNA methylation pattern Mesenchymal tumors had the highest amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH tumors the lowest. There were no significant differences for CD68+ cells, FoxP3+ cells and PD-1 expression between groups. Systemically, there was a relative increase of CD8+ T cells and CD8+ PD-1 expression and a relative decrease of CD4+ T cells after radiochemotherapy in all subgroups except IDH tumors. Overall survival was the longest in the IDH group (median 36 months), intermediate in RTK II tumors (27 months) and significantly lower in mesenchymal and RTK I groups (15.5 and 16 months respectively). Conclusions Methylation based stratification of GBM is related to T cell infiltration and survival, with IDH and mesenchymal tumors representing both ends of a spectrum. DNA methylation profiles could be useful in stratifying patients for immunotherapy trials.

PAX5 haploinsufficiency induces low T cell infiltration in the cancer microenvironment via reduced chemokines

2021 ◽  
Vol 21 ◽  
Author(s):  
Lei Wang ◽  
Xue Liang ◽  
Mi Liang ◽  
Dang Li ◽  
Jia Gu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Gene Editing ◽  
Immune Escape ◽  
Cell Infiltration ◽  
Loss Of Function ◽  
Wild Type ◽  
T Cell Infiltration ◽  
Wild Type Control

Aims: To investigate the effects of PAXT mutations on tumor immunity. Background: Loss of function of PAX5 plays a key role in PAX5 mutation tumor. Objective: PAX5 haploinsufficiency promoting tumorigenesis is related to immune escape, but there was no report about mechanisms of PAX5 mutation inducing tumor immunological escape. Method: We constructed the PAX5 haplodeletion A20 cell lines using gene-editing technology, built allografted A20 tumor models and evaluated the effect of PAX5 haplodeletion on T cells and chemokines in the tumor microenvironment (TME). Result: Our results from different methods indicated percentages of CD3+ CD4+ T cells and CD3+ CD8+ T cells in TME of PAX5 haplodeletion clones decreased significantly compared with that of PAX5 wild type control. Several chemokines, such as Ccl2, Ccl4, Cxcl9 and Cxcl10, in TME of PAX5. Conclusion: Our study showed that PAX5 haploinsufficiency induced low T cell infiltration in TME using decreased chemokines.

scholarly journals Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Minjun Du ◽  
Yicheng Liang ◽  
Zixu Liu ◽  
Xingkai Li ◽  
Mei Liang ◽  
...  
Keyword(s):  
Risk Assessment ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Assessment Model ◽  
Cell Infiltration ◽  
Risk Assessment Model ◽  
T Cell Infiltration ◽  
Key Genes

BackgroundCD8+ T cells are one of the central effector cells in the immune microenvironment. CD8+ T cells play a vital role in the development and progression of lung adenocarcinoma (LUAD). This study aimed to explore the key genes related to CD8+ T-cell infiltration in LUAD and to develop a novel prognosis model based on these genes.MethodsWith the use of the LUAD dataset from The Cancer Genome Atlas (TCGA), the differentially expressed genes (DEGs) were analyzed, and a co-expression network was constructed by weighted gene co-expression network analysis (WGCNA). Combined with the CIBERSORT algorithm, the gene module in WGCNA, which was the most significantly correlated with CD8+ T cells, was selected for the subsequent analyses. Key genes were then identified by co-expression network analysis, protein–protein interactions network analysis, and least absolute shrinkage and selection operator (Lasso)-penalized Cox regression analysis. A risk assessment model was built based on these key genes and then validated by the dataset from the Gene Expression Omnibus (GEO) database and multiple fluorescence in situ hybridization experiments of a tissue microarray.ResultsFive key genes (MZT2A, ALG3, ATIC, GPI, and GAPDH) related to prognosis and CD8+ T-cell infiltration were identified, and a risk assessment model was established based on them. We found that the risk score could well predict the prognosis of LUAD, and the risk score was negatively related to CD8+ T-cell infiltration and correlated with the advanced tumor stage. The results of the GEO database and tissue microarray were consistent with those of TCGA. Furthermore, the risk score was higher significantly in tumor tissues than in adjacent lung tissues and was correlated with the advanced tumor stage.ConclusionsThis study may provide a novel risk assessment model for prognosis prediction and a new perspective to explore the mechanism of tumor immune microenvironment related to CD8+ T-cell infiltration in LUAD.

scholarly journals Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci

2019 ◽  
Vol 316 (6) ◽  
pp. H1480-H1494 ◽  
Author(s):  
Maria M. Xu ◽  
Antoine Ménoret ◽  
Sarah-Anne E. Nicholas ◽  
Sebastian Günther ◽  
Eric J. Sundberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Antigen Recognition ◽  
Cell Infiltration ◽  
Antigen Specificity ◽  
Effector Cells ◽  
T Cell Infiltration

Effector CD8 T cells infiltrate atherosclerotic lesions and are correlated with cardiovascular events, but the mechanisms regulating their recruitment and retention are not well understood. CD137 (4–1BB) is a costimulatory receptor induced on immune cells and expressed at sites of human atherosclerotic plaque. Genetic variants associated with decreased CD137 expression correlate with carotid-intimal thickness and its deficiency in animal models attenuates atherosclerosis. These effects have been attributed in part to endothelial responses to low and disturbed flow (LDF), but CD137 also generates robust effector CD8 T cells as a costimulatory signal. Thus, we asked whether CD8 T cell-specific CD137 stimulation contributes to their infiltration, retention, and IFNγ production in early atherogenesis. We tested this through adoptive transfer of CD8 T cells into recipient C57BL/6J mice that were then antigen primed and CD137 costimulated. We analyzed atherogenic LDF vessels in normolipidemic and PCSK9-mediated hyperlipidemic models and utilized a digestion protocol that allowed for lesional T-cell characterization via flow cytometry and in vitro stimulation. We found that CD137 activation, specifically of effector CD8 T cells, triggers their intimal infiltration into LDF vessels and promotes a persistent innate-like proinflammatory program. Residence of CD137+ effector CD8 T cells further promoted infiltration of endogenous CD8 T cells with IFNγ-producing potential, whereas CD137-deficient CD8 T cells exhibited impaired vessel infiltration, minimal IFNγ production, and reduced infiltration of endogenous CD8 T cells. Our studies thus provide novel insight into how CD137 costimulation of effector T cells, independent of plaque-antigen recognition, instigates their retention and promotes innate-like responses from immune infiltrates within atherogenic foci. NEW & NOTEWORTHY Our studies identify CD137 costimulation as a stimulus for effector CD8 T-cell infiltration and persistence within atherogenic foci, regardless of atherosclerotic-antigen recognition. These costimulated effector cells, which are generated in pathological states such as viral infection and autoimmunity, have innate-like proinflammatory programs in circulation and within the atherosclerotic microenvironment, providing mechanistic context for clinical correlations of cardiovascular morbidity with increased CD8 T-cell infiltration and markers of activation in the absence of established antigen specificity. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/effector-cd8-t-cells-seed-atherogenic-foci/ .

scholarly journals Reversing Epigenetic Gene Silencing to Overcome Immune Evasion in CNS Malignancies

2021 ◽  
Vol 11 ◽  
Author(s):  
Nivedita M. Ratnam ◽  
Heather M. Sonnemann ◽  
Stephen C. Frederico ◽  
Huanwen Chen ◽  
Marsha-Kay N. D. Hutchinson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Immune Evasion ◽  
Immune Cell ◽  
Single Agent ◽  
Cell Infiltration ◽  
Cell Trafficking ◽  
T Cell Infiltration ◽  
Dismal Prognosis

Glioblastoma (GBM) is an aggressive brain malignancy with a dismal prognosis. With emerging evidence to disprove brain-immune privilege, there has been much interest in examining immunotherapy strategies to treat central nervous system (CNS) cancers. Unfortunately, the limited success of clinical studies investigating immunotherapy regimens, has led to questions about the suitability of immunotherapy for these cancers. Inadequate inherent populations of tumor infiltrating lymphocytes (TILs) and limited trafficking of systemic, circulating T cells into the CNS likely contribute to the poor response to immunotherapy. This paucity of TILs is in concert with the finding of epigenetic silencing of genes that promote immune cell movement (chemotaxis) to the tumor. In this study we evaluated the ability of GSK126, a blood-brain barrier (BBB) permeable small molecule inhibitor of EZH2, to reverse GBM immune evasion by epigenetic suppression of T cell chemotaxis. We also evaluated the in vivo efficacy of this drug in combination with anti-PD-1 treatment on tumor growth, survival and T cell infiltration in syngeneic mouse models. GSK126 reversed H3K27me3 in murine and human GBM cell lines. When combined with anti-PD-1 treatment, a significant increase in activated T cell infiltration into the tumor was observed. This resulted in decreased tumor growth and enhanced survival both in sub-cutaneous and intracranial tumors of immunocompetent, syngeneic murine models of GBM. Additionally, a significant increase in CXCR3+ T cells was also seen in the draining lymph nodes, suggesting their readiness to migrate to the tumor. Closer examination of the mechanism of action of GSK126 revealed its ability to promote the expression of IFN-γ driven chemokines CXCL9 and CXCL10 from the tumor cells, that work to traffic T cells without directly affecting T maturation and/or proliferation. The loss of survival benefit either with single agent or combination in immunocompromised SCID mice, suggest that the therapeutic efficacy of GSK126 in GBM is primarily driven by lymphocytes. Taken together, our data suggests that in glioblastoma, epigenetic modulation using GSK126 could improve current immunotherapy strategies by reversing the epigenetic changes that enable immune cell evasion leading to enhanced immune cell trafficking to the tumor.

scholarly journals Global pattern of CD8+ T cell infiltration and exhaustion in colorectal cancer predicts cancer immunotherapy response

2020 ◽  
Author(s):  
Sun Tian ◽  
Fulong Wang ◽  
Rongxin Zhang ◽  
Gong Chen
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cell Infiltration ◽  
Global Pattern ◽  
Cell Exhaustion ◽  
T Cell Infiltration

Abstract MSI/MSS status does not fully explain cancer immunotherapy response in colorectal cancer. We used gene expression data of 454 samples (MSI=131, MSI-L=23, MSS=284, Unknown=16) and developed a method TMEPRE that models colorectal cancer specific signature of CD8+ T cell infiltration and CD8+ T cell exhaustion states. TMEPRE showed predictive power in three datasets of anti-PD1 treated patients(p=0.056, 0.115, 0.003). CD8+ T cell exhaustion component of TMEPRE model correlates with anti-PD1 responding progenitor exhausted CD8+ T cells in both tumor and viral infection(p=0.048, 0.001). Global pattern of TMEPRE on 454 colorectal cancer samples indicated that 10.6% of MSS patients and 67.2% of MSI patients show biological characters that can benefit from anti-PD1 treatment. Within MSI nonresponders, approximately 50% showed no sufficient amount of tumor infiltrating CD8+ T cells and 50% showed terminal exhaustion of CD8+ T cells. These terminally exhausted CD8+ T cells coexisted with signature of myeloid-derived suppressor cells in colorectal cancer.

Regulatory T Cells Prevent Effector T Cell Infiltration Into GvHD Target Tissue by Affecting Chemokine Signaling.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1341-1341 ◽  
Author(s):  
Brie Turner ◽  
Shaheda Ahmed ◽  
Sarah Pagan ◽  
Jean Norden ◽  
Matthew Collin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Chemokine Receptors ◽  
Effector T Cells ◽  
Cell Infiltration ◽  
Cell Surface Expression ◽  
Effector T Cell ◽  
T Cell Infiltration

Abstract Abstract 1341 Poster Board I-363 Introduction Graft versus host disease (GVHD) following haematopoietic stem cell transplantation is often first observed in the skin; a primary target organ of GVHD. GVH related tissue damage in the skin is mainly driven by infiltrating alloreactive cytotoxic effector T cells, facilitated by a cascade of cytokines and chemokines. Our recently published observations showed that addition of regulatory T cells (Treg) suppressed skin GVH tissue damage mediated by alloreactive CD8+ T cells in an in vitro human GVHD skin explant model [1]. The current study investigated the role of Treg in modulating effector T cell infiltration into skin, it's consequence on the severity of skin GVH histopathology and the possible changes of effector T cell production and expression of chemokines and chemokine receptors. Methods CD8+ T cells, monocyte derived dendritic cells (mDC) and natural Treg (CD4+CD2highFOXP3+) were generated as previously described [1]. In an in vitro human GVHD skin explant model, CD8+ T cells and ex vivo expanded Treg obtained from buffy coats were used as “donor” cells. mDC and skin biopsies obtained from HLA unmatched unrelated normal volunteers acted as “recipient” tissues. “Donor” CD8+ T cells primed with “recipient” mDC in the presence or absence of Treg were co-cultured with “recipient” skin. The severity of histopathological GVH skin damage was scored as grade 0 to grade IV using a clinically validated scoring system. The number of infiltrating CD8+ T cells in skin was evaluated using immunohistochemistry then correlated to the severity of skin GVH histopathology. The gene expression of selected chemokines and chemokine receptors in alloreactive CD8+ effector T cells was analysed using quantitative RT-PCR. The effector T cell expression of chemokine receptors was assessed using flow cytometry. The secretion of selected chemokines into the culture supernatants was quantified using BD cytometric bead array kit. Results The percentage of infiltrating effector T cells in skin was significantly associated with the severity of skin GVH histopathology (2.6±0.8, 12.6±3.1 and 27.2±2.7 for skin sections with GVH histopathology grade I, II and III-IV; p=0.017 and 0.021 respectively). The percentage of skin infiltrating CD8+ T cells was significantly reduced by the presence of Treg (24.8±3.7 vs 11.58±1.8, p=0.011, n=13) which correlated with Treg mediated suppression of skin GVH histopathology (p<0.0001, n=13). The presence of Treg also down-regulated effector T cell expression of chemokine/chemokine receptor genes (CCL3, CCL5, CCR4, CCR5, CXCL10 and CXCL11) that are involved in the recruitment of effector T cells to GVH target tissues. Further analysis indicated a trend toward reduced effector T cell surface expression of CCR4 and CCR5 (31.9±4.3 vs 12.5±2.7; 13.7±1.8 vs 8.8±4.1 respectively, n=3) in the presence of Treg. There was also a reduction in CX3CR1 and cutaneous lymphocyte associated antigen (CLA) (11.1±1.9 vs 2.2±0.6; 34.6%±7.0 vs 11.6±2.2 respectively, n=3). The effector T cell surface expression of CXCR3, CCR2 and CCR10 was very low regardless of the presence or absence of Treg. Release of CCL3, CCL5, CXCL9 and CXCL10 into the culture supernatant was strongly suppressed by the presence of Treg (813±122 vs 77±30; 816±248 vs 405±148; 5517±967 vs 974±540 and 858±209 vs 195±57, p=0.001, 0.065, 0.002 and 0.015 respectively, n=8). However, CXCL11 and CX3CL1 levels were below detectable limits regardless of the presence or absence of Treg. Conclusions Ex vivo expanded natural Treg can inhibit CD8+ effector T cell infiltration into skin which correlated with Treg suppression of cytotoxic T cell mediated skin GVH histopathology in an in vitro human GVHD model. This effect may be attributed to a decrease in chemokine and chemokine receptor interactions mediated by Treg. These observations indicate a potential mechanism for Treg mediated GVHD suppression. [1] X N Wang et al., Transplantation 2009 Disclosures No relevant conflicts of interest to declare.

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