TIGIT expression

The GBM Pathomics model constructed based on the pathohistological features of H&E-stained sections well predicted the expression level of TNFRSF9 molecules in THCA.

Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8+ T cells.

Multivariate logistic regression analyses revealed the association of high percentage of TIGIT+ TCM γδ T cells with an increased risk of poor induction chemotherapy response. In this study, we investigated the distribution of γδ T cells and their memory subsets in patients with non-M3 AML and suggested TIGIT+ TCM γδ T cells as potential predictive markers of induction chemotherapy response.

Building on our past findings of increased TIGIT+KLRG1+ TEX with teplizumab therapy in type 1 diabetes (T1D), in the absence of treatment we found that the frequency of TIGIT+KLRG1+ TEX is stable within an individual but differs across individuals in both T1D and healthy control (HC) cohorts. Moreover, the frequency of TIGIT+KLRG1+ TEX was significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig). The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of TEX may be more effective in DR4 subjects and TEX may be indirectly influenced by cellular interactions that are blocked by abatacept.

In contrast, Fcs anti-TIGIT did not deplete human Treg in vitro and was associated with anecdotal objective clinical responses in two Phase I solid tumor cancer patients in whom peripheral Treg frequencies remained stable on treatment. Collectively, these data provide evidence of pharmacological activity and anti-tumor efficacy of anti-TIGIT antibodies lacking the ability to engage FcγR.

Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.

P2, N=29, Terminated, Hoffmann-La Roche | Active, not recruiting --> Terminated; Sponsor's decision to terminate the study after Stage 1; will not proceed with Stage 2.

However, the magnitude of 89Zr-αTIGIT uptake in tumor, relative to the IgG tracer was minimal. These findings highlight the features and limitations of using 89Zr-αTIGIT to visualize TIGIT in the GBM microenvironment.

PD-1+ Tregs accumulation in bone marrow in higher leukemic burden setting was linked to lactate acid secreted by AML blasts and decreased after disease remission. Our findings provided a novel insight into Tregs in AML and possible mechanism for resistance of PD-1 blockade in AML.

Anti-TIGIT MOA-related genes and signatures correlated with efficacy in ociperlimab + tislelizumab-treated 1L PD-L1+ NSCLC. Combining anti-TIGIT MOA-related factors with PD-L1 expression identified a subgroup of patients with improved efficacy.Table. Efficacy Analyses in Patient SubgroupsCutoff: aTop 1/3; bMedian; cTC≥25%

Collectively, these results showed that the MGMT unmethylation and high levels of CD47 and TIGIT are associated with a poor prognosis in ADG. Patients with high CD47 and TIGIT expression may benefit from anti-CD47 and TIGIT immunotherapy.

Dual blockade of TIGIT and programmed death-1 (PD-1) increased the cytotoxicity of GD2-CARTs to some extent, suggesting that low TIGIT and PD-1 expression of GD2-CARrejTs is a major factor required for robust cytotoxicity against SCLC. Not only for robust cytotoxicity but also for availability as "off-the-shelf" T cell therapy, iPSC-derived GD2-CARrejTs are a promising novel treatment for SCLC.

We concluded that TIGIT+NK cells competitively bind to PVR with CD226 and promote NK cell depletion. Anti-PD-1 decreases PVRL1 expression through PD-1/PD-L1 pathway, reducing the PVR/TIGIT inhibitory signal pathway, and enhancing function of PVR/CD226 activation signal.

Yet, a strong positive correlation of TIGIT expression with CD8+ infiltrates was only detected in cutaneous squamous cell carcinoma (p < 0.01), but not keratoacanthomas. Providing a comprehensive overview on the collective landscape of inhibitory immune checkpoint expression, this study reveals associations of novel inhibitory immune checkpoint with CD8+ immune infiltrates and tumour differentiation and highlights the TIGIT/CD155 axis as a potential new target for cutaneous squamous cell carcinoma immunotherapy.

Some chemotherapeutic drugs such as oxaliplatin (OXA) can cause tumor immunogenic cell death (ICD), activate immunity, and realize chemoimmunotherapy for tumors...OXA@TIGIT showed good efficacy in several cancer models, leading to tumor regression, effectively inhibiting tumor growth and prolonging mouse survival. Furthermore, the OXA@TIGIT MVs activate a strong tumor-specific immune response in the body, providing long-term (more than 2 months) protection from tumor reactivation in the B16F10 melanoma rechallenge mouse model.

High levels of TIGIT induced the alteration of CD4+ T cell based immunomodulation and predicted poor prognosis of LUAD patients. Therefore, TIGIT can be potential biomarker for LUAD.

Our findings identified TIGIT as a promising therapeutic target for LUAD. LUAD could benefit more from the combined therapy of IL-15 stimulation and TIGIT blockade.

This preliminary study reports significant changes in gene expression for oral melanoma between canine patients with localized disease relative to those with metastatic disease. In the future, a more in-depth investigation involving immunohistochemistry analysis and single-cell RNA expression is necessary to confirm our findings.

Our research findings strongly suggest that CD155/TIGIT represents a promising therapeutic target for treating TNBC.

Our analysis shows that RRP tissue shows elevated levels of multiple immune check point targets and VEGFR3, with varied patterns unique to each papilloma patient. Some of these immune checkpoint markers already have novel immunotherapies available or in development, providing molecular rationale to offer these systemic treatments to selected patients affected by RRP alongside VEGF inhibitors. Laryngoscope, 2024.

Our research also highlights that GFI treatment has the dual effect of restoring and activating CD8T cells, achieved through the downregulation of TIGIT expression and the upregulation of Granzyme B. Taken together, our findings suggest that GFI treatment effectively eliminates PMN-MDSCs in the spleen, leading to a reduction in MDSC numbers in circulation and tumor tissues, ultimately enhancing the antitumor immune response of CD8T cells and inhibiting tumor growth. This study introduces a promising therapeutic agent for breast cancer.

T cells co-expressing PD-1 and TIGIT represent potential targets for EC immunotherapy. Dual immune checkpoint blockade targeting PD-1 and TIGIT may offer an effective therapeutic strategy for EC, providing valuable insights for the development of immunotherapeutic approaches.

Chronic lymphocytic leukemia/small lymphocytic lymphoma and anaplastic large cell lymphoma demonstrated high TME TIGIT expression compared with PD-L1, with a high proportion of dual TIGIT and PD-L1-positivity. Our results are likely to contribute to the design and correlative study of therapeutic response in clinical trials targeting TIGIT alone or in combination with PD1/PDL1.

TIGIT KO in ex vivo expanded NK cells increased their cytotoxicity and metabolic fitness and prevented NK-cell fratricide when combined with Fc-active anti-TIGIT antibodies. These fratricide-resistant TIGIT KO NK cells have therapeutic potential alone or in combination with Fc-active anti-TIGIT antibodies to enhance their efficacy.

In addition, we discovered that 4-1BB correlates with TIGIT expression, the agonism of which contributes to TIGIT immunotherapy. Overall, our data suggest that in GBM, TIGIT acts as a regulator of a complex network, and provide new clues about its use as an immunotherapeutic target.

This exploratory work highlighted that PD1 was the most represented checkpoint. TIGIT was the second most represented checkpoint while ICOS, TIM3 and LAG3 were 3 other checkpoints whose expression was found to be less important. ILT2 and OX40 appeared to be weakly expressed.

“Furthermore, our data shows the positivity of TIGIT in 88% of patients, demonstrating the presence of this immune checkpoint in the bone marrow microenvironment. These data will need to be confirmed in a larger group of patients, but they open up the possibility of new target treatments in multiple myeloma

Further studies employing the VISTA antibody and siRNA are in progress. This will form the basis of employing anti-VISTA therapy in the future clinical trials of ICI therapy in Ph(-) MPN.

TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.

Fourth, targeting this PD1+/TIGIT+ exhausted CD8+ T cell population with immune checkpoint monoclonal antibody inhibitors reduced CD8+ T cell tumoral recruitment, Ccl4 production, and optic glioma growth. Collectively, these findings establish an obligate role for PD-1+/TIGIT+ CD8+ T cells in Nf1-optic glioma control and suggest that immune checkpoint modulation may be useful for the treatment of LGGs in children.

Furthermore, these alterations cannot be restored by telbivudine treatment but can be partially restored by IL-21 and anti-TIGIT stimulation...It enhanced IFN-γ production in splenic NK cells rather than intrahepatic NK cells, indicating a brand-new mechanism of IL-21 in HBV clearance when combined with anti-TIGIT. Overall, our findings contribute to the design of immunotherapy through enhancing the antiviral efficacy of NK cells in chronic HBV infection.

Controllable variables include the timing of collection (earlier or later in the clinical course), alternative growth factor usage, enrichment or depletion of cell populations in the graft, or post-transplant growth factor administration. We suggest that the aHSCT graft can be thought of as an immunotherapy tool and not just for hematopoietic recovery.

These results also suggest that MEZI may be useful in combination with other agents for increasing immune activation and reducing immune exhaustion. Further analyses comparing the effect of different CELMoDs on the BM TME are ongoing.

Distinct signatures of T-cell exhaustion and depletion are present in the early post-ASCT period among individuals relapsing within 24 months. Peripheral blood immune phenotyping may identify functionally high-risk patient populations in need of alternative treatment approaches to maintain durable disease control.

Our findings demonstrated that leukemia exposure led to altered NK cell frequency and maturation distribution as demonstrated by reduced immature and an increased tolerant and cytotoxic fraction. Changes in the expression profile of activating and inhibitory receptors were also observed. Therefore, we concluded that the leukemic environment leads to NK dysfunction and that strategies that aim to control NK maturation and the interaction between stem cell ligands and functional NK receptors can be explored to restore immunosurveillance in JAK2V671F Myeloproliferative Neoplasms.

Patients responding to tec exhibited a differential immune profile in early cycles compared with nonresponders, with greater transient T-cell activation. In contrast, an exhausted T-cell phenotype was sustained in nonresponders during the first 2 treatment cycles. While mutations in BCMA cannot be excluded, we did not detect BCMA loss as a mechanism of relapse, but observed a dysfunctional immune phenotype at PD, with increased T-cell exhaustion and higher frequency of gamma delta T cells and immunosuppressive Tregs.

The most significant advantage of iPSC-derived T cell therapy lies in its clonality and potential for an unlimited supply of therapeutic T cells. Additional gene-editing of iPSC-derived CARrejT cells could potentially lay the groundwork for allogeneic, "off-the-shelf" GD2-CARrejT therapy, thereby introducing a promising new therapeutic avenue for patients with ENKL in the foreseeable future.

Importantly, we demonstrate two major findings: (1) that a possibly more efficacious anti-BCMA CAR-T product can be manufactured from cryopreserved, mobilized apheresis material regardless of storage time and (2) cryopreserved preASCT samples may expand autologous CAR-T cell therapy access to heavily treated patients with poor T cell quality. CLF & JAM contributed equally

This deeper understanding of the immunological landscape in RT patients sheds light on the interplay between T cell subsets and treatment response in RT, paving the way for personalized therapeutic strategies. Further validation and exploration can lead to improved outcomes and tailored interventions for RT.

Additionally, 52% had prior exposure to anti-BCMA therapies, including belantamab mafodotin (31%), anti-BCMA CAR T-cell therapies (37%), and anti-BCMA bispecific antibody therapies (4%), with some having exposure to multiple prior anti-BCMA therapies (17%). Tec is an effective therapy in RRMM with a slightly lower efficacy observed in patients with prior anti-BCMA therapy exposure. PFS reductions among these anti-BCMA exposed patients may be partly due to independent disease associated risk factors. A pre-Tec peripheral blood T-cell population enriched with highly cytotoxic effector T-cells was associated with response to therapy, while suppressive TIGIT+Tregs were associated with nonresponse, suggesting a potential therapeutic role for TIGIT blockade or CD25+ cell depletion to enhance the therapeutic efficacy of bispecific antibodies.

On this basis, we investigated if inhibition of cyclin D1/CDK4 with palbociclib (CDK4/6 inhibitor) could reprogram recurrent MCL to deepen and prolong the ibrutinib (BTK inhibitor) response in a phase I clinical trial, and the resistance mechanism by longitudinal genomic analysis of sequential samples from individual patients in the context of the clinical response. In one resistant patient, this led to the maintenance of CD4+ and CD8+ T effector memory cells and a CR in response to venetoclax plus BTKi for nearly 3 years and continuing. In summary, by integrated longitudinal scRNA-seq analysis of a hypothesis-driven therapy, we have provided the first evidence that 1) MCL cells comprise 4 major transcriptomically distinct clusters; 2) resistance to CDK4/6i is associated with expansion of C2 that fuels the proliferating C4 MCL cells, or the long-lived C3 MCL cells with elevated BCL2 expression; 3) CDK4/6i harnesses BTKi response by promoting the maintenance of effector memory T cells; 4) combined inhibition of BCL2 and BTK overrides resistance to CDK4/6i and BTKi, leading to a durable clinical response; and 5) T cell surveillance is pivotal for a durable response to CDK4/6, BTK or BCL2 inhibition; implicating genome-guided combination therapy to overcome therapy resistance in MCL.

In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.