CD27 expression

We revealed that CD27 expression levels serve as an indicative marker for the prognosis of MM patients. The CD27- PERK-ATF4 is a promising target for the treatment of MM.

P2, N=50, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Nov 2023

P2, N=50, Not yet recruiting, PETHEMA Foundation

They may be involved in the suppression of intestinal aging and longevity through anti-tumor immunity, elimination of senescent cells and stressed cells in the aging environment. This finding could be a breakthrough in aging research.

Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.

Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

• Analysis of IL-17A production post γδ T-cell expansion. This protocol is used in: Science Advances (2022), DOI: 10.1126/sciadv.abm9120.

DNA methylation is involved in CD27 expression in cancer. CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers.

Most malignant cells (91.6 %) expressed CD44, but only 50 % of the patients had CD27 expressed. The positive CD 44 expression was associated with unfavorable prognostic markers, including a decrease.

Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel) in ZUMA-7...Higher baseline and postinfusion levels of serum inflammatory markers associated with differentiated/effector products, reduced efficacy, and increased CRS and neurologic events, thus suggesting targets for intervention. These data support better outcomes with earlier CAR T-cell intervention and may improve patient care by informing on predictive biomarkers and development of next-generation products.

Interestingly, both dtCD70-Fc and dtCD70-Fc(D265A) were effective in prolonging the survival of mice harbouring BCL1 B cell lymphoma, demonstrating that a substantial part of the stimulatory activity of dtCD70-Fc in this setting is retained in the absence of FcγR interaction. These data reveal that TNFRSF ligands can be generated with a tunable activity profile and suggest that this class of immune agonists could have broad applications in immunotherapy.

© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Acknowledgments. GB was supported by Fundación Alfonso Martín Escudero.

Patients received 3 days of fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) followed by a single dose of CBG-002 infusion...Nine patients developed G1/2 CRS, which resolved spontaneously except for 2 patients who required steroids and tocilizumab, and no patients developed G3/4 CRS or ICANS... In this phase I study, CBG-002, a CD27-armored BCMA-CAR T therapy has demonstrated remarkable safety and clinical activity in RRMM patients.

Methods Samples were obtained from large B cell lymphoma (LBCL) patients that were part of the TRANSCEND-NHL-001 trial (NCT02631044, Abramson et al, Lancet 2020).Thirty-two patients with r/r B-cell lymphoma who received CAR-T cell treatment lisocabtagene maraleucel (16 responders (R) and 16 non-responders (NR)) were included in our analyses and (metabolically) analyzed by flow cytometry and extracellular flux analysis...More specifically, a higher abundance of memory phenotypes, metabolic activity and mitochondrial biogenesis of both harvested T cells and CAR-T product associates with improved clinical response. Combining metabolic, phenotypical and clinical characteristics and biomarkers of patient T cells (both pre- or post-production) shows the importance of the metabolic phenotype and fitness of T cell starting material, underlying the importance of early line CAR T therapy following diagnosis.

Moreover, different monoclonal antibodies (Abs) and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab, ArgenX) that activates FcγR-expressing effector cells to assess the therapeutic potential of targeting CD70 in MM... Our results indicate that CD70-expressing MM cells have a stem-cell like phenotype and propagate the disease. Targeting CD70 is a promising new therapy especially in advanced disease.

In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively...A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models...IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.

In patients, with subsequent progression of the MGUS the initially low expression of CD27, CD19, CD95 and high expression CD56, CD117, CD200 were more often determined. Patients with the CD117 (+) marker, even with the number of tumor PCs in the bone marrow ≤3%, progressed more often (p = 0.001) than patients without this marker. Determining these markers can help identify patients with high risk of MGUS progression.

Furthermore, FACS analysis demonstrated a significant increase in the proportion of CD8+ T cells relative to CD4+ T cells in these patients. Conclusions Ongoing experiments are currently investigating the distribution of CAF subpopulations producing COL1A1 and their correlation with the response to CAR T cell therapy.

In the tumor microenvironment, overexpression of CD2/CD27 inhibited the activation of nitrogen metabolism pathways and suppressed M2 polarization of macrophages, thereby preventing brain metastasis of breast cancer.

CD27 overexpression will suppress the viability of the KYSE150 and TE3 cells. Our findings suggested that the degree of CD27 expression could serve as an esophageal cancer prognosis biomarker.

In summary, inflammation, and the immune response play an important role in OSCC. All five hub genes were good predictors of OSCC prognosis, suggesting that they could be used as potential therapeutic targets and tumor markers.

Primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy. Laboratory staff should pay more attention to and recognize the pleomorphic morphology of neoplastic plasma cells, which can enable timely clinical development of bone marrow smear, biopsy, flow cytometry, and cytogenetic tests providing help in early diagnosis and treatment.

By providing insights into the widely divergent immunologic profiles of LNENs, our results might serve as a basis for the development of novel immunotherapy-related approaches in these devastating malignancies.

We are currently evaluating further improvements of our protocol by additional depletion markers.ConclusionWe optimized our DCC enrichment method by depletion of CD27-positive and CD319-positive cells, the major confounders for the specific detection of EpCAM positive DCC in BM. The enrichment factor by adding additional depletion markers is currently assessed.

TSCMs marker CD27 and CD95 were both indicators of survival in patients with colon cancer. Thus, it is believed that TSCMs represent a desirable population for future use in combination immunotherapy.

Taken together, this study supports the role of immune checkpoint molecules and implicates the TNFR superfamily as key players in immunotherapy response in our cohort of HNSCC. Validation of these findings in a prospective study is required to determine the robustness of these tissue signatures.

A preliminary data shows an underlying CD27 deficiency on CD3 may be associated with chronic and not recent EBV infection in children with B cell lymphoid malignancy. The study will be pursued to get a larger sample size as a high frequency of EBV positivity is noted in this studied patients B cell acute lymphoblastic leukemia, Hemophagocytic Lymphohistiocytosis (HLH), EBV, CD27

In this regard, different Abs and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab) that activates FcγR-expressing effector cells... Although the treatment options of MM have rapidly increased during the last years, MM remains an incurable disease that ultimately leads to death. Our results indicate that especially advanced MM stages express high levels of CD70. In addition, our results indicate that CD70/CD27 cell-autonomous signaling contributes to disease progression and therapy resistance and identifies CD70 as potential target in MM.

In summary, ADI-270 demonstrates preclinical proof-of-concept of an armored allogeneic CD70 γδ CAR T cell therapy utilizing the CD27 natural receptor CAR format for targeting CD70+ cancers. These data support continued development and further investigation of ADI-270 in the clinic.

These results provided the cellular mechanism of IL-2-driven differentiation when expanding therapeutic T cells, revealing the critical need to refine manufacturing procedures and preserve CD27-expressing CAR T cells. This work also suggested the potential of CD27 as a biomarker for the functional quality of CAR T cell products.

When co-cultured with the autologous tumor cell lines, mbIL15-engineered TIL secreted higher levels of IFN-γ and induced higher cytotoxicity as compared to unengineered TIL cultured with IL-2. Taken together, these data demonstrate that mbIL15-engineered TIL can successfully be expanded from comparatively “cold” tumors with low T-cell infiltration, such as CRC and sarcoma, while maintaining high TCR diversity and polyfunctionality and demonstrating higher cytokine production and cytotoxic activity against autologous tumor lines, compared to conventional TIL with IL2.

When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination... Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

We conclude that the percentage of CD8+ T cells out of all CD8+ T cells has the potential to serve as a biomarker for predicting the risk of CMV reactivation during RT of the brain. Furthermore, this study highlights the importance of taking the CMV serostatus into account when analyzing T cells and their subsets.

Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL.

CD70 mainly regulates tumor immune escape by regulating T cell-mediated tumor killing, with Tregs possibly being its primary T cell subset. Our first pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of the CD70-CD27 signaling axis in different tumors.

BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools.

Our data show that AIM2 promotes IgG-producing B cells and circulating GL7 + B cells in a potentially novel inflammasome-independent role in cGVHD. We are investigating how AIM2 affects alloantibody production in cGVHD B cell so that therapeutic targets can be identified.

Our findings suggest that CD70 can play a role in either tumour suppression or oncogenesis in DLBCL, likely via distinct immune evasion mechanisms, that is, impairing T cell priming or inducing T cell exhaustion. Characterisation of specific dysfunction of CD70 in DLBCL may thus provide opportunities for the development of novel targeted immuno-therapeutic strategies.

The expression level of CD27 in HNSCC may significantly influence the prognosis of patients with HNSCC. Radiomics based on contrast-enhanced CT is potentially effective in predicting the expression level of CD27.

In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.