The Feature of δRec-ψJα sjTRECs Level and Frequency of 23 TCR Vβ-Dβ1 sjTRECs in Mononuclear Cells, CD4+ and CD8+ T Cells from Cord Blood and Peripheral Blood of Normal Individuals.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3873-3873
Author(s):  
Yangqiu Li ◽  
Qingsong Yin ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Grzegorz Przybylski ◽  
...  
Keyword(s):  
T Cells ◽  
Quantitative Analysis ◽  
Cord Blood ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Output Function ◽  
Cd4 Cells ◽  
Cd8 Cells ◽  
Normal Individuals

Abstract Thymic recent output function is characterized its importance of thymus to T-cell diversity in the periphery of both children and adults. The generation of TCR diversity occurs in the thymus through recombination of gene segments encoding the variable parts of the TCR α and β chains. During these processes, by-products of the rearrangements are generated in the form of signal joint T-cell receptor excision circles (sjTRECs), which is considered as a very valuable tool to estimate thymic function. Quantitative of δRec-ψJα sjTRECs can direct evaluate the recent thymic output function, but it is unable to analyze the particular thymic output function of different TCR Vβ subfamily naive T cells. The complexity of TCR Vβ repertoire is an important factor for immune reconstitution, quantitative analysis of series TCR Vβ-Dβ sjTRECs could be used to evaluate the levels of different Vβ subfamily naive T cells. In the present study, quantitative analysis of δRec-ψJα sjTRECs was performed in mononuclear cells, CD3+, CD4+ and CD8+T cells from peripheral blood of normal individuals and cord blood by real-time PCR(TaqMan). And the analysis of 23 TCR Vβ-Dβ1 sjTRECs was performed by semi-nested PCR. Different amounts of DNA (corresponding to 2*105, 5*104, 1*104 and 1*103 cells respectively) from all samples were amplified to estimate the frequency of TCR Vβ-Dβ sjTRECs. The mean value of δRec-ψJα sjTRECs was detected in 4.10±3.65/1000 PBMCs, 6.37±5.28/1000 CD3+cells, 3.28±1.24/1000 CD4+cells, 4.67±3.63/1000 CD8+cells from normal individuals (n=14) and 35.59±47.56/1000 CBMC, 71.48±86.42/1000 CD3+cells, 41.02±32.9/1000 CD4+ cells, 52.05±52.32/1000 CD8+cells from cord blood (n=9) (p=0.0208, p=0.0096, p=0.0003, p=0.0026, respectively). A part of Vβ subfamily sjTRECs could be detected in all samples from cord blood (Vβ2, 3, 4, 5, 10, 13, 14, 15, 19 and 22) and peripheral blood (Vβ10, 13 and 14) at 5*104 cells level, some of Vβ subfamily sjTRECs could be detected in 1*103 cells level. The frequencies of 23 Vβ-Dβ1 sjTRECs were different at the same cellular concentration. The number of detectable Vβ subfamily sjTRECs was 22.00±0.94/2×105, 18.8±1.87/5×104, 10.40±2.99/1×104 and 0.78±1.39/1×103 CBMCs, as compared with 18.70±2.45/2×105 (p=0.002), 13.7±2.67/5×104 (p<0.001), 5.5±2.07/1×104 (p=0.001) and 0.50±0.71/1×103 (p=0.739) in PBMCs from normal individuals. Similar results were found in CD4+ and CD8+ T cells which were sorted from both CBMCs and PBMCs, the number of detectable Vβ subfamily sjTRECs was 13.90±2.38/1×104 CD4+cells, 11.5±1.96/1×104CD8+cells from cord blood and 5.6±2.68/1×104 CD4+cells (p<0.001) and 8.2±2.57/1×104CD8+cells (p>0.005) from normal individuals. The results indicate that the number of detectable sjTRECs of Vβ subfamilies and the frequencies of most Vβ-Dβ1 sjTRECs in normal PBMCs, CD4+ and CD8+T cells were obviously lower than those in cord blood. In conclusions, the results provide the base data of naïve T cells levels and thymic recent output function in cord blood and peripheral blood of normail individuals in chinese.

Detection of sjTRECs within Peripheral Blood T Cells Evaluation of Recent Thymic Output Function in Myelodysplastic Syndrome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4919-4919
Author(s):  
Xin Du ◽  
Yang-qiu Li ◽  
Jian-yu Weng ◽  
Ze-sheng Lu ◽  
Rong Guo ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Output Function ◽  
Peripheral Blood Mononuclear ◽  
Thymic Output ◽  
Normal Individuals ◽  
Blood Mononuclear Cells ◽  
Immunological Abnormalities

Abstract Objective The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell disorders, while, immunological abnormalities are frequently observed in patients with MDS. Several reports revealed that about 10% of MDS patients have clinical autoimmune disorders like skin vasculitis, rheumatic disease, or autoimmune hemolytic anemia. Furthermore, serological immunological abnormalities like hyper- or hypogammaglobulinemia, positivities of antinuclear antibody, positivities of direct Coombs test, or inverted CD4/8 ratios were found in 18–65% of patients with MDS. Recently immunosuppressive therapies including prednisolone, antithymocyte globulin, and cyclosporin A (CsA) are used to treat cytopenia in some patients with MDS. But it isn’t very clear the immunosuppressive mechanism in MDS and the value of the treatment. To analyze the content of signal joint Tcell receptor excision DNA circles signal joint T cell receptor excision DNA circles(sjTRECs) within peripheral blood mononuclear cells (PBMCs), thereby to infer the level of naive T cells and the recent thymic output function in patients with myelodyspoastic syndrom. Methods Quantitative detection of sjTRECs in DNA of peripheral blood mononuclear cells from 13 normal individuals and 8 patienets were performed by real-time polymerase chain reaction (PCR) and TaqMan technique. Results The median value of sjTRECs copies P1 000 PBMCs was 4.37±3.64 in normal individuals whereas it was1.07 ±1.40 copies P1 000 PBMCs in myelodysplastic syndrom patients (P &lt;0. 05). Conclusions MDS Patients decrease in recent thymic output function.

Surface Expression of PR1 Peptide on Thymic Dendritic Cells Does Not Eliminate PR1-Specific CD8+ Cells In Umbilical Cord Blood

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 959-959
Author(s):  
Lisa S St. John ◽  
Karen Clise-Dwyer ◽  
Rebecca Patenia ◽  
Anna Sergeeva ◽  
Elizabeth J. Shpall ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cord Blood ◽  
Cd8 T Cells ◽  
Umbilical Cord Blood ◽  
Peripheral Blood ◽  
Negative Selection ◽  
Fetal Thymus ◽  
Central Tolerance ◽  
Cd8 Cells

Abstract Abstract 959 Positive and negative selection of developing thymocytes is mediated primarily by cortical and medullary epithelial cells (CEC and MEC), respectively, in the thymus. Tolerance to peripheral tissue antigens (PTA) not normally expressed in the thymus can result when PTA expression is induced by AIRE in MEC or when corticomedullary dendritic cells (DC) present endogenous antigens, both mechanisms contributing to deletion of potentially auto-reactive T cells. However, in some instances, negative selection may be incomplete, leading to the release of autoreactive cells into the periphery. Indeed, T cells specific for PR1, the HLA-A2-restricted self-peptide derived from proteinase 3 (P3) and neutrophil elastase (NE), are present in peripheral blood of healthy adults, albeit at extremely low frequency of fewer than 0.0005% of CD8+ T cells. This suggests there is strong thymic central tolerance to PR1. However, PR1-CTL can increase from 0.1 to 2% of peripheral blood CD8 T cells in CML patients treated with interferon or stem cell transplant, and similar levels can be achieved after PR1 peptide vaccination, which suggests that under some circumstances this central tolerance can be reversed. Because of the increasing use of umbilical cord blood (UCB) as an alternative donor source and because incomplete graft-versus-leukemia (GVL) immunity after UCB transplant contributes to relapse, we sought to determine whether PR1-CTL can be expanded from UCB. We hypothesized that PR1-CTL frequency should be low in UCB due to central tolerance. Surprisingly, we found PR1-CTL at a frequency ranging from 0.007 to 0.345% (mean 0.117%) of CD8+ cells in 57 HLA-A2+ cord blood units, similar to what is observed in immunologically responsive vaccine patients and 100- to 1000-fold higher than in healthy adults. The PR1-CTL were predominantly CCR7+CD45+CD28+ and did not efficiently expand ex vivo following peptide stimulation and low dose IL-2, which was consistent with a naive T cell subset. Therefore, this data suggests that central tolerance to PR1 is incomplete. To study whether PR1 is expressed in human thymus, we used the PR1/HLA-A2-specific antibody 8F4 to study PR1 expression. Thymic CEC and MEC expressed no P3, NE, or PR1 by flow cytometry or immunofluorescence imaging of sectioned fetal thymus, which is consistent with previous reports showing absence of P3 or NE induction by AIRE in MEC. Interestingly, by flow cytometric analysis, we found that PR1 is expressed on the surface of thymic dendritic cells (DC) exclusively. This selective expression of PR1 was further confirmed via immunoflourescent staining of sectioned fetal thymus, and the PR1-expressing DC were localized to the corticomedullary junction and medulla. Thus it appears that PR1 expression by DC in the thymus is insufficient for complete central tolerance to PR1. Furthermore, because we have previously shown that PR1-overexpressing CML cells can induce apoptosis of high affinity PR1-CTL, it is possible that peripheral tolerance mechanisms are most critical for preventing autoreactivity to PR1 in humans. These observations suggest possible strategies to overcome tolerance to PR1 by modifying DC uptake and cross-presentation of soluble P3 and NE, when selective autoimmunity may be desirable for leukemia patients or detrimental for patients with vasculitis such as Wegener's granulomatosis. Disclosures: No relevant conflicts of interest to declare.

Detection of 24 TCR Vβ-Dβ1 sjTRECs in T Cells from Cord Blood, Peripheral Blood of Normal Individuals and Patients with AML-M2.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4557-4557
Author(s):  
Yangqiu Li ◽  
Qingsong Yin ◽  
Shaohua Chen ◽  
Lijian Yang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Peripheral Blood ◽  
Output Function ◽  
Thymic Function ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Thymic Output ◽  
Normal Individuals

Abstract Thymic function is characterized its importance of thymus to T-cell diversity in the periphery of both children and adults during both health and disease. The generation of TCR diversity occurs in the thymus through recombination of gene segments encoding the variable parts of the TCRα and β chains. During these processes, by-products of the rearrangements are generated in the form of signal joint T-cell receptor excision circles (sjTRECs). As sjTRECs are stable extrachromosomal DNA fragments, are not replicated during mitosis and thus diluted with each round of cell division, and are therefore most frequent in naïve T cells that have recently left the thymus, their quantification is actually considered as a very valuable tool to estimate thymic function. Quantitative of δRec-ψJα sjTRECs can direct evaluate the recent thymic output function, but it is unable to analyze the particular thymic output function of different TCR Vβ subfamily naive T cells. The complexity of TCR Vβ repertoire is an important factor for immune reconstitution, it should be established the quantitative analysis of series TCR Vβ-Dβ sjTRECs to evaluate the levels of different Vβ subfamily naive T cells. In the present study, analysis of 24 TCR Vβ-Dβ sjTRECs was established by semi-nested PCR using 24 Vβ subfamily antisense primers and 2 Dβ1 sense primers. TCR Vβ-Dβ sjTRECs were amplified in genomic DNA from mononuclear cells of 10 cord blood samples, 10 cases of peripheral blood from normol individuals and 11 cases with AML-M2. Different amounts of DNA (corresponding to 2*105, 5*104, 1*104 and 1*103 cells respectively) from all samples were amplified to estimate the frequency of TCR Vβ-Dβ sjTRECs. The results showed that most Vβ subfamily sjTRECs could be detected in all samples from cord blood and peripheral blood at 2*105 or 5*104 cells level, some of Vβ subfamily sjTRECs could be detected in 1*103 cells level. Whereas the frequency of Vβ subfamily sjTRECs were lower in peripheral blood T cells from patients with AML-M2 than in normal individuals (p<0.05). Vβ19, Vβ23 and Vβ24 subfamily sjTRECs could not be detected in all samples at 5*104 cells level. The results indicated that Vβ subfamily naive T cells could be detected with different frequency in peripheral blood of normaol individuals as well as in some patients with AML-M2. Lower frequency of Vβ subfamily naive T cells was found in most AML-M2 patients.

scholarly journals EXTH-14. A NOVEL LONG-ACTING INTERLEUKIN-7 AGONIST, NT-I7, INCREASES CYTOTOXIC CD8 CELLS AND ENHANCES SURVIVAL IN MOUSE GLIOMA MODELS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii89-ii89
Author(s):  
Subhajit Ghosh ◽  
Ran Yan ◽  
Sukrutha Thotala ◽  
Arijita Jash ◽  
Anita Mahadevan ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cervical Lymph Nodes ◽  
Cd8 Cells ◽  
Interleukin 7 ◽  
Long Acting ◽  
Spleen And Lymph Nodes ◽  
Mouse Glioma

Abstract BACKGROUND Patients with glioblastoma (GBM) are treated with radiation (RT) and temozolomide (TMZ). These treatments can cause prolonged severe lymphopenia, which is associated with shorter survival. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 would protect T cells from treatment-induced lymphopenia and improve survival. METHODS C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-17 (10 mg/kg on the final day of RT completion). We followed for survival and profiled CD3, CD8, CD4, FOXP3 in peripheral blood over time. In parallel, we assessed cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. RESULTS Median survival in mice treated with NT-I7 combined with RT was significantly better than RT alone (GL261: 40d vs 34d, p&lt; 0.0021; CT2A: 90d vs 40d, p&lt; 0.0499) or NT-I7 alone (GL261: 40d vs 24d, p&lt; 0.008; CT2A: 90d vs 32d, p&lt; 0.0154). NT-17 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261 (40d vs 47d) and CT2A (90d vs 90d). NT-I7 treatment significantly increased the amount of CD8+ cells in the peripheral blood and tumor. NT- I7 rescued CD8+ T cells from RT induced lymphopenia in peripheral blood, spleen, and lymph nodes. NT-I7 alone or NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood and tumor while reducing the FOXP3+ T-reg cells in the tumor microenvironment. CONCLUSIONS NT-I7 protects T-cells from RT induced lymphopenia, improves cytotoxic CD8+ T lymphocytes systemically and in the tumor, and improves survival. Presently, a phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

565 A novel long-acting interleukin-7 agonist, NT-I7, increases cytotoxic CD8+ T cells and enhances survival in mouse glioma models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A599-A599
Author(s):  
Subhajit Ghosh ◽  
Ran Yan ◽  
Sukrutha Thotala ◽  
Arijita Jash ◽  
Anita Mahadevan ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Standard Of Care ◽  
Control Group ◽  
Cervical Lymph Nodes ◽  
Cd8 Cells ◽  
Interleukin 7 ◽  
Long Acting

BackgroundRadiation (RT) and temozolomide (TMZ), which are standard of care for patients with glioblastoma (GBM), can cause prolonged severe lymphopenia. Lymphopenia, in turn, is an independent risk factor for shorter survival. Interleukin-7 (IL-7) is a cytokine that is required for T cell homeostasis and proliferation. IL-7 levels are inappropriately low in GBM patients with lymphopenia. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 rescues treatment-induced lymphopenia and improves survival.MethodsImmunocompetent C57BL/6 mice bearing two intracranial glioma models (GL261 and CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-I7 (10 mg/kg on the final day of RT completion). We profiled the CD3, CD8, CD4, FOXP3 cells in peripheral blood over time. We also immunoprofiled cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. Survival was monitored daily.ResultsMedian survival in mice treated with NT-I7 combined with RT was significantly longer than RT alone (GL261: 40d vs 34d, p<0.0021; CT2A: 90d vs 40d, p<0.0499) or NT-I7 alone (GL261: 40d vs 24d, p<0.008; CT2A: 90d vs 32d, p<0.0154). NT-I7 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261(40d vs 47d) and CT2A (90d vs 90d). Cytotoxic CD8+ T cells were increased in both peripheral blood (0.66 x 105 to 3.34 x 105; P≤0.0001) and tumor (0.53 x 103 to 1.83 x 103; P≤0.0001) in mice treated with NT-I7 when compared to control. Similarly, NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood (0.658 x 105 to 1.839 x 105 P≤0.0001) when compared to RT alone. There were decreases in tumor infiltrating FOXP3+ T-reg cells in mice treated with NT-I7 (1.9 x 104 to 0.75 x 104 P≤0.0001) and NT-I7 + RT (1.9 x 104 to 0.59 x 104 P≤0.0001) when compared to the control group without NT-I7. In addition, NT- I7 treatment increased CD8+ T cells in thymus, spleen, and lymph nodes.ConclusionsNT-I7 enhances cytotoxic CD8+ T lymphocytes systemically and in the tumor microenvironment, and improves survival. A phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 180-183 ◽  
Author(s):  
Carl E. Mackewicz ◽  
Baikun Wang ◽  
Sunil Metkar ◽  
Matthew Richey ◽  
Christopher J. Froelich ◽  
...  
Keyword(s):  
T Cells ◽  
Antiviral Activity ◽  
Cd8 T Cells ◽  
Culture Media ◽  
Cd4 Cells ◽  
Antiviral Protein ◽  
Cd8 Cells ◽  
Cd8 Cell ◽  
Anti Hiv ◽  
Primary Granule

Abstract In HIV infection, CD8+ cells show cytotoxic and noncytotoxic anti-HIV activity. The latter function is mediated, at least in part, by a secreted antiviral protein, the CD8+ cell antiviral factor (CAF). Because antiviral effector molecules, such as perforin and granzymes, reside in the exocytic granules of CD8+ T cells, we examined the possibility that granules contain CAF-like activity. CD8+ cells from HIV-infected individuals showing strong CAF-mediated antiviral activity were induced to release their granule constituents into culture media. Within 1 hour of stimulation, high levels of granzyme B (a primary granule constituent) were found in the culture fluids of previously activated CD8+ cells. The same culture fluids contained no or very low amounts of CAF activity, as measured with HIV-infected CD4+ cells. Maximal levels of CAF activity were not observed until 5 or 7 days after stimulation, consistent with typical CAF production kinetics. In addition, extracts of granules purified from antiviral CD8+ cells did not show any CAF activity, whereas the cytoplasmic fraction of these cells showed substantial levels of antiviral activity. These findings suggest that CAF does not reside at appreciable levels in the exocytic granules of antiviral CD8+ T cells. (Blood. 2003;102: 180-183)

scholarly journals Quantitative analysis of hepatitis C virus-specific CD8+ T cells in peripheral blood and liver using peptide-MHC tetramers

1999 ◽  
Vol 96 (10) ◽  
pp. 5692-5697 ◽  
Author(s):  
X.-S. He ◽  
B. Rehermann ◽  
F. X. Lopez-Labrador ◽  
J. Boisvert ◽  
R. Cheung ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Quantitative Analysis ◽  
Hepatitis C ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Mhc Tetramers

scholarly journals IMMU-18. IMMUNOGENOMIC RESPONDER PHENOTYPE FROM A PHASE I TRIAL OF ANTI-LAG3 OR ANTI-CD137 ALONE AND IN COMBINATION WITH ANTI-PD-1 IN PATIENTS WITH RECURRENT GBM

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi122-vi123
Author(s):  
Christina Jackson ◽  
John Choi ◽  
JiaJia Zhang ◽  
Anna Piotrowski ◽  
Tobias Walbert ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Lower Percentage ◽  
Radiographic Evaluation ◽  
Peripheral Blood Mononuclear ◽  
Initial Resection

Abstract BACKGROUND Immune checkpoint inhibitors (ICIs) are not uniformly effective in glioblastoma treatment. Immunogenomic determinants may identify patients who are most likely to benefit from these therapies. Therefore, we compared the immunogenomic phenotype of a responder to combination anti-LAG-3 and anti-PD-1 therapy to non-responders. METHODS We performed T cell receptor (TCR) sequencing and gene expression analysis on pre-treatment, post-chemoradiation, and post-immunotherapy tumor specimens of glioblastoma patients treated with anti-LAG3 in combination with anti-PD-1 after first recurrence (NCT02658981, ongoing). We evaluated T cell clonotypes and immunophenotype of serially collected peripheral blood mononuclear cells (PBMCs) during treatment using multi-parametric flow cytometry. RESULTS To date, six patients have been enrolled in the initial anti-LAG-3 and anti-PD-1 cohort. One patient demonstrated complete response, one had stable disease, and four had progressive disease by radiographic evaluation. The responder demonstrated substantially higher TCR clonality in the resected tumor at initial diagnosis compared to non-responders (mean 0.028 vs. 0.005). Shared tumor infiltrating clonotypes with pre-immunotherapy PBMCs exhibited an increase in frequency from initial resection (6.8%) to resection at recurrence (20%). The responder’s tumor at initial resection exhibited increased gene signatures of PD1low CD8+ T cells, chemokine signaling, and interferon gamma pathways. On PBMC phenotypic analysis, the responder demonstrated significantly higher percentages of CD137+ CD8+T cells (median 8.38% vs 3.24%, p=0.02) and lower percentages of Foxp3+CD137+ CD4+T cells compared to non-responders (median 18.5% vs. 38.5%, p=0.006). Interestingly, dynamic analysis of PBMCs showed that the responder demonstrated a lower percentage of PD1+ CD8+ T cells pre-immunotherapy (median 2.5% vs.12.4%, p=0.002), with persistent decrease over the course of treatment while non-responders showed no consistent pattern. CONCLUSION Our preliminary results demonstrate significant differences in tumor and peripheral blood immunogenomic characteristics between responder and non-responders to anti-LAG3 and anti-PD-1 therapy. These immunogenomic characteristics may help stratify patients’ response to combination ICIs.

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