Immune profile of metastatic uveal melanoma during treatment with pembrolizumab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9536-9536
Author(s):  
Ernesto Rossi ◽  
Ilaria Zizzari ◽  
Giovanni Schinzari ◽  
Alessandra Di Filippo ◽  
Brigida Anna Maiorano ◽  
...  
Keyword(s):  
T Cells ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Immune Checkpoints ◽  
Soluble Form ◽  
Immunological Parameters ◽  
Blood Samples ◽  
Low Levels ◽  
Potential Factors

9536 Background: Metastatic uveal melanoma (mUM) is a rare and aggressive disease. No standard therapy has been established. All the available treatments derive from trials in cutaneous melanoma. A minority of patients with mUM can benefit from immunotherapy. Immunological features of a group of patients with metastatic UM treated with Pembrolizumab were analyzed in order to explore the immune-response in this disease and the potential factors able to select the patients who can benefit from immunotherapy. Methods: Blood samples from 12 UM patients before (T0) and during treatment with Pembrolizumab (T1: after 1 cycle of Pembrolizumab; T2: after 3 cycle of Pembrolizumab) were collected. Peripheral blood mononucleated cells (PBMCs) were isolated and characterized for markers expression. Sera were analyzed for a panel of soluble (s) immune checkpoints and cytokines. The correlation between immunological parameters with PFS and OS was explored. Blood samples from 6 metastatic cutaneous melanoma (CM) patients with a confirmed response to anti PD-1 agents were also collected during the treatment and analyzed for PBMCs and sera. Results: Soluble CTLA4, sPD-L1, sCD137, sTIM3 were significantly higher in UM than in CM. CD137 was significantly higher in UM patients progressed with Pembrolizumab than in the 2 responsive patients (512 pg/ml vs < 12.9 pg/ml, respectively, p = 0.04) who are still alive and on treatment after a median follow-up of 24 months. Low sGITR, sCD137, sHVEM, and sTIM3 are associated with longer PFS. IL-8 was lower in CM than UM (2.5 pg/ml vs 40.7 pg/ml) and in the responsive versus progressed UM patients (3,7 pg/ml vs 118 pg/ml, p = 0,042). Low levels of IL-8 and IL-1-alpha are significantly associated with longer PFS (p = 0.011 and 0.010 respectively). In responsive patients CD137 expression on CD3+, CD4+ and CD8+ T cells was higher than in progressed patients, while sCD137 was absent. Conclusions: A group of s-immune checkpoints and cytokines correlate with Pembrolizumab effectiveness in mUM. High expression of CD137 on T cells associated with the absence of its soluble form in responders could suggest the correlation between the retention of this co-stimulatory molecule and efficacy of anti-PD1.

scholarly journals Immunoexpression of Macroh2a in Uveal Melanoma

2019 ◽  
Vol 9 (16) ◽  
pp. 3244 ◽  
Author(s):  
Salvatorelli ◽  
Puzzo ◽  
Bartoloni ◽  
Palmucci ◽  
Longo ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Cutaneous Melanoma ◽  
High Expression ◽  
Melanoma Metastasis ◽  
Proper Treatment ◽  
Immunohistochemical Expression ◽  
Prognostic Role

MacroH2A is a histone variant whose expression has been studied in several neoplasms, including cutaneous melanomas (CMs). In the literature, it has been demonstrated that macroH2A.1 levels gradually decrease during CM progression, and a high expression of macroH2A.1 in CM cells relates to a better prognosis. Although both uveal and cutaneous melanomas arise from melanocytes, uveal melanoma (UM) is biologically and genetically distinct from the more common cutaneous melanoma. Metastasis to the liver is a frequent occurrence in UM, and about 40%–50% of patients die of metastatic disease, even with early diagnosis, proper treatment, and close follow-up. We wanted to investigate macroH2A.1 immunohistochemical expression in UM. Our results demonstrated that mH2A.1 expression was higher in metastatic UM (21/23, 91.4%), while only 18/32 (56.3%). UMs without metastases showed mH2A.1 staining. These data could suggest a possible prognostic role for mH2A.1 and could form a basis for developing new pharmacological strategies for UM treatment.

Expression of soluble DC-HIL/gpnmb receptor in the blood of metastatic non-small cell lung carcinoma treated with anti-PD1/PDL1 monoclonal antibodies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14038-e14038
Author(s):  
Jin-Sung Chung ◽  
Vijay Ramani ◽  
Masato Kobayashi ◽  
Vinita Popat ◽  
Ponciano D Cruz ◽  
...  
Keyword(s):  
T Cells ◽  
Advanced Nsclc ◽  
Soluble Form ◽  
Clinical Samples ◽  
Blood Levels ◽  
Cell Lung Carcinoma ◽  
Excellent Outcome ◽  
Ifn Γ ◽  
Low Levels ◽  
Nsclc Patients

e14038 Background: Anti-PD1/PDL1 therapy benefits only a minority (10-20%) of treated NSCLC. Identifying markers distinguishing responders vs. non-responders will improve management of NSCLC. DC-HIL receptor is a new checkpoint whose inhibitory mechanisms are divergent from the PD1 pathway. Tumor cells express DC-HIL receptor and its soluble form (sDC-HIL). We tested whether sDC-HIL expression regulates NSCLC response to anti-PD1/PDL1 Ab using animal models and human clinical samples. Methods: Tet-Off controlled sDC-HIL-transfected LL2 lung cancer cells were i.v. injected into mice (lung mets) and treated with doxycycline (Dox). Day 6, mice were sorted into 2 groups with/without Dox and treated with i.p. 200 μg Ab, every 2 d /6 shots. Day 18, # of lung-LL2 cells were counted by FACS and IFN-γ+ T cells in tumors analyzed. Advanced NSCLC patients (n = 51) treated with immune checkpoint inhibitors were every 6 weeks evaluated for partial response (PR), stable (SD) and progressive disease (PD) by RECIST. Serum were collected on weeks 0, 2, and 6 and assayed for sDC-HIL amounts by ELISA. Results: In mice treated with Dox (halt sDC-HIL expression), anti-PDL1 Ab treatment markedly reduced lung mets and increased IFN-γ+ T cells (p < 0.001), whereas this excellent outcome was not noted in Dox-untreated mice (induce sDC-HIL). For NSCLC, PD1/PDL1 therapy produced PR (n = 3), SD (n = 25) and PD (n = 23) at week 6. sDC-HIL blood levels at week 0 did not correlate with tumor size, but the levels at week 6 of PD patients were significantly higher than PR/SD patients (8.4 ± 5.6 vs. 4.0 ± 1.6 ng/ml, p = 0.001, Mann-Whitney test) and healthy donors (2.6 ± 0.9 ng/ml). Most patients (26 out of 30 cases) showed fluctuation in sDC-HIL levels during treatment. PD-patients (14/15 cases) showed increasing or persistently elevated levels ( > 4 ng/ml), with one case at low levels ( < 4 ng/ml). SD/PR-patients (13/15) had decreasing or persistently low levels, with 2 exceptions with high levels in all time points. Conclusions: sDC-HIL blood level may serve as a biomarker to indicate tumor-resistance of advanced NSCLC patients to PD1/PDL1 therapy. The degree and direction of sDC-HIL fluctuation may be useful to predict prognosis for NSCLC.

Molecular profiling and clinical characteristic of malignant melanoma in younger patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22087-e22087
Author(s):  
Jomjit Chantharasamee ◽  
Karlton Wong ◽  
Bartosz Chmielowski
Keyword(s):  
Gene Expression ◽  
General Population ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Stage I ◽  
Stage Iii ◽  
Younger Patients ◽  
Adjuvant Immunotherapy ◽  
Better Than

e22087 Background: Combination of clinical and molecular data has not yet been well established in adolescent and younger adult patients with melanoma Methods: We performed a retrospective analysis of the molecular profiles and clinical outcome of patients diagnosed at the age younger than 40 treated at UCLA during 2010 to 2019. Patient’s molecular profile, characteristics, and treatment outcome were described using descriptive statistic. Kaplan-Meier curve was used for disease-free survival (DFS) and overall survival (OS). Results: 150 patients with a median age of 29 year (12-39) were analyzed. 101 (67.3%) patients had cutaneous melanoma, 49 (32.7%) had localized uveal melanoma. Of those 101, 23.8% had pre-existing benign or congenital nevus. 70/101 (69.3%) was stage I-II, 26/101 (25.7%) stage III and 5/101 (4.9%) stage IV. Of those 37 patients with molecularly characterized tissue, 23 (62%) had BRAF mutation including 17 V600E, 4 V600 unknown codon, 2 G469A, 2 NRAS and 1 NF-1 mutation. 11/37 were BRAF negative. 79.6% of patients who were not tested were stage I. For patients with stage III, 16/26 (61%) received adjuvant immunotherapy, none of adjuvant targeted therapy. At 35.1 months follow-up time, 27/96 (28%) localized cutaneous melanoma experienced relapse. 1-year DFS was 73% in adjuvant vs. 90% in no adjuvant immunotherapy group. Among 49 uveal melanoma patients, the median age was 27 years old. 23/49 (49%) had a T1 tumor, 18/49 (36.7%) T2, 6/49(12.2%) T3, 1/49(2%) T4. At 45 months follow-up time, three (6.1%) patients developed metastasis. 5-year DFS and OS was 90% and 100%, respectively. 45 patients had tissue for gene expression profiling and/or FISH testing. 15/45 (33%) had class IA, 13/45 (28%) had class IB, and 8/45 (17.7%) had class 2. 24 samples were analyzed by FISH: 14 with disomy 3, 5 with complex disomy 3 with gain of chromosome 6 or 8, and 5 with monosomy 3. Conclusions: Similarly to general population, most of younger patients with melanoma are diagnosed with stage I disease. Among patients with stage III melanoma treated with adjuvant immunotherapy 1-year DFS was comparable to the general population. Patients with stage III who did not receive adjuvant therapy had an excellent DFS which confirms that the decision on selecting patients for treatment was appropriate. The prognosis of younger patients with uveal melanoma was much better than predicted by molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.

Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood But Not in the Skin of Patients With Small Plaque Parapsoriasis

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1409-1417 ◽  
Author(s):  
J. Marcus Muche ◽  
Ansgar Lukowsky ◽  
Jürgen Heim ◽  
Markus Friedrich ◽  
Heike Audring ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Clone ◽  
Small Plaque ◽  
Blood Samples ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone

Clinical, immunohistological, and molecular biological data suggest the chronic dermatosis small plaque parapsoriasis (SPP) to be a precursor of mycosis fungoides (MF). However, most data are contradictory and confusing due to inexact definition of SPP. Recently, clonal T cells were detected in skin and blood samples of early MF. Because demonstration of identical T-cell clones in skin and blood of SPP patients would indicate a close relationship of SPP to MF, we investigated the clonality of skin and blood specimens from 14 well-defined SPP patients. By a polymerase chain reaction (PCR) amplifying T-cell receptor γ rearrangements and subsequent high-resolution electrophoresis, clonal T cells were detected in 9 of 14 initial and 32 of 49 follow-up blood samples, but in 0 of 14 initial skin specimens. Even a clone-specific PCR showing the persistence of the initial blood T-cell clone in 20 of 20 follow-up samples, failed to detect the T-cell clone in the skin. In 2 patients, the clonal T cells were shown to be CD4+. For the first time, the majority of SPP patients was shown to carry a T-cell clone in the peripheral blood. Although a relation between circulating clonal T cells and SPP cannot directly be proven by the applied techniques, our results indicate blood T-cell clonality to be a characteristic feature of SPP and CTCL because analysis of multiple controls and clinical workup of our SPP patients excluded other factors simulating or causing a clonal T-cell proliferation. A sufficient cutaneous antitumor response but also an extracutaneous origin of the T-cell clones might explain the failure to detect skin infiltrating clonal T cells.

scholarly journals Paucity of CD4+ CCR5+ T Cells May Prevent Transmission of Simian Immunodeficiency Virus in Natural Nonhuman Primate Hosts by Breast-Feeding

2008 ◽  
Vol 82 (11) ◽  
pp. 5501-5509 ◽  
Author(s):  
Ivona Pandrea ◽  
Richard Onanga ◽  
Sandrine Souquiere ◽  
Augustin Mouinga-Ondéme ◽  
Olivier Bourry ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Replication ◽  
Simian Immunodeficiency Virus ◽  
Breast Feeding ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Natural Hosts ◽  
Low Levels ◽  
Lower Expression

ABSTRACT Simian immunodeficiency virus (SIV) persistence in wild populations of African nonhuman primates (NHPs) may occur through horizontal and vertical transmission. However, the mechanism(s) and timing of the latter type of transmission have not been investigated to date. Here we present the first study of SIV transmissibility by breast-feeding in an African NHP host. Six mandrill dames were infected with plasma containing 300 50% tissue culture infective doses of SIVmnd-1 on the day after delivery. All female mandrills became infected, as demonstrated by both plasma viral loads (VLs) and anti-SIVmnd-1 seroconversion. Neither fever nor lymphadenopathy was observed. At the peak of SIVmnd-1 viral replication (days 7 to 10 postinoculation), plasma VLs were high (8 × 106 to 8 × 108 RNA copies/ml) and paralleled the high VLs in milk (4.7 × 104 to 5.6 × 105 RNA/ml). However, at the end of the breast-feeding period, after 6 months of follow-up, no sign of infection was observed for the offspring. Later on, during a 4-year follow-up examination, two of the offspring showed virological evidence of SIVmnd-1 infection. Both animals seroconverted at least 6 months after the interruption of lactation. In conclusion, despite extensive viral replication in mandrill mothers and high levels of free virus in milk, no SIVmnd-1 transmission was detectable at the time of breast-feeding or during the following months. Since we observed a markedly lower expression of CCR5 on the CD4+ T cells of young mandrills and African green monkeys than on those of adults, we propose that low levels of this viral coreceptor on CD4+ T cells may be involved in the lack of breast-feeding transmission in natural hosts of SIVs.

Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood But Not in the Skin of Patients With Small Plaque Parapsoriasis

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1409-1417 ◽  
Author(s):  
J. Marcus Muche ◽  
Ansgar Lukowsky ◽  
Jürgen Heim ◽  
Markus Friedrich ◽  
Heike Audring ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Clone ◽  
Small Plaque ◽  
Blood Samples ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone

Abstract Clinical, immunohistological, and molecular biological data suggest the chronic dermatosis small plaque parapsoriasis (SPP) to be a precursor of mycosis fungoides (MF). However, most data are contradictory and confusing due to inexact definition of SPP. Recently, clonal T cells were detected in skin and blood samples of early MF. Because demonstration of identical T-cell clones in skin and blood of SPP patients would indicate a close relationship of SPP to MF, we investigated the clonality of skin and blood specimens from 14 well-defined SPP patients. By a polymerase chain reaction (PCR) amplifying T-cell receptor γ rearrangements and subsequent high-resolution electrophoresis, clonal T cells were detected in 9 of 14 initial and 32 of 49 follow-up blood samples, but in 0 of 14 initial skin specimens. Even a clone-specific PCR showing the persistence of the initial blood T-cell clone in 20 of 20 follow-up samples, failed to detect the T-cell clone in the skin. In 2 patients, the clonal T cells were shown to be CD4+. For the first time, the majority of SPP patients was shown to carry a T-cell clone in the peripheral blood. Although a relation between circulating clonal T cells and SPP cannot directly be proven by the applied techniques, our results indicate blood T-cell clonality to be a characteristic feature of SPP and CTCL because analysis of multiple controls and clinical workup of our SPP patients excluded other factors simulating or causing a clonal T-cell proliferation. A sufficient cutaneous antitumor response but also an extracutaneous origin of the T-cell clones might explain the failure to detect skin infiltrating clonal T cells.

scholarly journals The Effect of LatentToxoplasma gondiiInfection on the Immune Response in HIV-Infected Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ondrej Beran ◽  
Petr Kodym ◽  
Marek Maly ◽  
Alzbeta Davidova ◽  
Gabriela Reinvartova ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Group Analysis ◽  
Hiv Disease ◽  
Immunological Parameters ◽  
Hla Dr ◽  
Changes Over Time ◽  
Kinetics Of

A relationship between latent toxoplasmosis and the immune system during HIV disease is poorly understood. Therefore, the aim of this follow-up study was to characterize immunological parameters in HIV-infected patients with latent toxoplasmosis and noninfected individuals. A total of 101 HIV-infected patients were enrolled in the study. The patients were classified into two groups based on anti-Toxoplasma gondiiantibodies: a group of 55 toxoplasma-positive persons (TP) and a group of 46 toxoplasma-negative persons (TN). Absolute counts of several lymphocyte subsets decreased in the TP group, namely, T cells (p=0.007), B cells (p=0.002), NK cells (p=0.009), CD4 T cells (p=0.028), and CD8 T cells (p=0.004). On the other hand, the percentage of CD8 T cells expressing CD38 and HLA-DR significantly increased during the follow-up in the TP group (p=0.003,p=0.042, resp.) as well as the intensity of CD38 and HLA-DR expression (MFI) on CD8 T cells (p=0.001,p=0.057, resp.). In the TN group, analysis of the kinetics of immunological parameters revealed no significant changes over time. In conclusion, the results suggest that latentT. gondiiinfection modulates the immune response during HIV infection.

scholarly journals A 3-Week Dynamic Differences of Immunological Parameters in Severe and Non-severe COVID-19

2020 ◽  
Author(s):  
Qiang Li ◽  
Wei Xu ◽  
Weixia Li ◽  
Chenglu Huang ◽  
Liang Chen
Keyword(s):  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Immunological Parameters ◽  
T Lymphocyte Subsets ◽  
Cytokine Profiles ◽  
Tnf Α ◽  
Severe Group ◽  
Ifn Γ ◽  
Low Levels

Abstract Objective We aimed to compare the dynamic differences of immunological parameters in severe and non-severe COVID-19. Methods In this study, the cytokine profiles and lymphocyte subsets of 70 patients (31 severe COVID-19 and 39 non-severe COVID-19) were longitudinally analyzed. Results Compared with non-severe cases, severe cases had higher age (64 vs 36 years, p<0.001), more common comorbidities (74.2% vs 15.4%, p<0.001), and more frequently lymphopenia (0.7 vs 1.6×109/L, p<0.001). Severe cases had markedly higher levels of IL-6, IL-8, and IL-10 than non-severe cases from baseline to 3 weeks after admission (p<0.001). No significant differences were observed in the levels of IL-1β, IL-2, IL-4, IL-5, IL-12P70, IL-17, TNF-α, IFN-α, and IFN-γ between the two groups during the follow-up (p > 0.05). The absolute numbers of CD3+, CD4+, CD8+, and CD45+ T cells were markedly lower in severe cases compared with that in non-severe cases from baseline to 3 weeks after admission (p<0.001). The decrease of T lymphocyte subsets reached its peak from day 1 to 3 after admission, and gradually increased from day 4 to 21 in the non-severe group; however, reached its peak from day 4 to 7 after admission, and sustained at a low levels in the severe group. Conclusion The dynamic changes of cytokine profiles and T lymphocyte subsets are related with the disease severity of patients with COVID-19.

scholarly journals A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8+ T cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zijun Wang ◽  
Mou Peng
Keyword(s):  
T Cells ◽  
Cutaneous Melanoma ◽  
Prognostic Biomarker ◽  
Normal Skin ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Tcr Signaling ◽  
Pathways Analysis ◽  
And Function

AbstractLymphocyte cytosolic protein 2 (LCP2) is one of the SLP-76 family of adapters, which are critical intermediates in signal cascades downstream of several receptors. LCP2 regulates immunoreceptor signaling (such as T-cell receptors) and is also required for integrin signaling in neutrophils and platelets. However, the role of LCP2 in the tumor microenvironment is still unknown. In this study, we found a significant increase of mRNA and protein expression of LCP2 in metastatic skin cutaneous melanoma compared to normal skin. The upregulation of LCP2 was associated with good overall survival of patients with metastatic skin cutaneous melanoma, who received pharmacotherapy and radiation. GSEA signaling pathways analysis showed that LCP2 was involved in multiple pathways of immune response and correlation analysis revealed LCP2 was positively correlated with molecules in TCR signaling and 11 immune checkpoints, while LCP2 negatively correlated with 2 immune checkpoints in the metastatic skin cutaneous melanoma. According to the different expressions of LCP2, high LCP2 expression was positively correlated with more tumor-infiltrating CD8+ T cells. Furthermore, Kaplan–Meier plot indicated that LCP2 acted as a prognostic biomarker for progression-free survival of patients with metastatic skin cutaneous melanoma receiving anti-PD1 immunotherapy. In conclusion, our results integrated both the expression and function of LCP2 in melanoma using multiple tools, shedding light on the potential role of LCP2 in melanoma, and suggesting LCP2 serves as a prognostic biomarker and therapeutic target in anti-tumor immunity.

scholarly journals Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis

2020 ◽  
Author(s):  
Mengzhou Guo ◽  
Feifei Yuan ◽  
Feng Qi ◽  
Jialei Sun ◽  
Qianwen Rao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Prognostic Significance ◽  
Normal Liver ◽  
Immune Checkpoints ◽  
Patient Stratification ◽  
Combination Strategies ◽  
Low Levels

Abstract Background FGL1-LAG-3 pathway is a promising immunotherapeutic target and has synergistic effect with PD-1/PD-L1. However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unkonwn. Method The distributions, associations, and clinical significances of LAG-3, FGL1, PD-L1 and CD8 protein expression in 143 HCC patients were assessed by multiplex immunofluorescence. Results We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3 + cells but not PD-L1. CD8 + T cells densities had positive correlation with PD-L1 levels and negative asscociation with FGL1 expression. Elevated densities of LAG-3 + cells and low levels of CD8 + T cells were correlated with poor disease outcome.Moreover,LAG-3 + cells deteriorated patient stratification based on the abundance of CD8 + T cells. Paitents with positive PD-L1 expression on tumor cells (PD-L1TC + ) tended to have a improved survival than that with negative PD-L1 expression on tumor cells (PD-L1TC - ). Futhermore, PD-L1TC - in combination with high densities of LAG-3 + cells showed the worst prognosis, and PD-L1TC + patients with low densities of LAG-3 + cells had the best prognosis. Conclusions LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3 + cells and CD8 + T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively. Levels of LAG-3 + cells in combination with PD-L1 status on tumor cells have potential to identify patients who may benefit from immune checkpoints blockade combination strategies.

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