scholarly journals Cellular and humoral Immune response to mRNA COVID-19 vaccination in subjects with chronic lymphocytic leukemia

2021 ◽  
Author(s):  
Zoe L Lyski ◽  
Myung Sun Kim ◽  
David Xthona Lee ◽  
Hans-Peter Raue ◽  
Vikram Raghunathan ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
B Lymphocyte ◽  
Strong Association ◽  
Significant Risk ◽  
Protective Role ◽  
Lymphocytic Leukemia ◽  
Humoral Immune ◽  
Immunocompromised Hosts

Chronic Lymphocytic Leukemia (CLL) is predominantly a B-lymphocyte leukemia associated with immune defects that are often exacerbated by CLL directed therapies. SARS-CoV-2 infection poses a significant risk of illness or mortality to CLL patients, and while SARS-CoV-2 vaccines are highly effective in immunocompetent individuals, efficacy varies substantially in immunocompromised patients, including those with CLL. To date, studies of COVID-19 vaccine immune responses in immunocompromised hosts have largely relied on semi-quantitative antibody titers that only partially characterize vaccine-elicited immune responses and do not measure B or T-cell specific responses that may also play a protective role in vaccinees. Here, we report RBD-specific antibody as well as B-cell and T-cell responses in an observational cohort of sixteen CLL subjects who received mRNA vaccination against SARS-CoV-2, finding a strong association between CLL treatment and vaccine immunogenicity, with important implications for vaccination timing in the context of CLL treatment or recovery from prior treatment.

Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1057-1063 ◽  
Author(s):  
Wendelina J. M. Mackus ◽  
Florine N. J. Frakking ◽  
Annette Grummels ◽  
Laila E. Gamadia ◽  
Godelieve J. de Bree ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cytotoxic T Cells ◽  
Lymphocytic Leukemia ◽  
The Absolute ◽  
Cell Chronic Lymphocytic Leukemia

Abstract In patients with B-cell chronic lymphocytic leukemia (B-CLL), the absolute number of T cells is increased. Although it has been suggested that these T cells might be tumor specific, concrete evidence for this hypothesis is lacking. We performed a detailed immunophenotypic analysis of the T-cell compartment in the peripheral blood of 28 patients with B-CLL (Rai 0, n = 12; Rai I-II, n = 10; Rai III-IV, n = 6) and 12 healthy age-matched controls and measured the ability of these patients to mount specific immune responses. In all Rai stages a significant increase in the absolute numbers of CD3+ cells was observed. Whereas the number of CD4+ cells was not different from controls, patients with B-CLL showed significantly increased relative and absolute numbers of CD8+ cells, which exhibited a CD45RA+CD27- cytotoxic phenotype. Analysis of specific immune responses with tetrameric cytomegalovirus (CMV)–peptide complexes showed that patients with B-CLL had significantly increased numbers of tetramer-binding CMV-specific CD8+ T cells. The rise in the total number of CD8+ cytotoxic T cells was evident only in CMV-seropositive B-CLL patients. Thus, our data suggest that in patients with B-CLL the composition of T cells is shifted toward a CD8+ cytotoxic cell type in an effort to control infections with persistent viruses such as CMV. Moreover, they offer an explanation for the high incidence of CMV reactivation in CLL patients treated with T cell–depleting agents, such as the monoclonal antibody (mAb) alemtuzumab (Campath; α-CD52 mAb). Furthermore, because in CMV-seronegative patients no increase in cytotoxic CD8+ T cells is found, our studies do not support the hypothesis that tumor-specific T cells account for T-cell expansion in B-CLL.

Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection

2019 ◽  
Vol 69 (10) ◽  
pp. 1752-1756 ◽  
Author(s):  
Govindakarnavar Arunkumar ◽  
Santhosha Devadiga ◽  
Anita K McElroy ◽  
Suresh Prabhu ◽  
Shahin Sheik ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
B Lymphocyte ◽  
Nipah Virus ◽  
Disease Onset ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune

Abstract Background Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors. Methods Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells. Conclusions We describe for the first time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

scholarly journals Dual B and T markers in acute and chronic lymphocytic leukemia

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 16-20
Author(s):  
KA Foon ◽  
RJ Billing ◽  
PI Terasaki
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Surface Membrane ◽  
Lymphocytic Leukemia ◽  
Rosette Formation ◽  
Leukemic Cells ◽  
Cell Markers ◽  
Membrane Immunoglobulin

Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell surface membrane markers. B-cell markers included surface membrane immunoglobulin, erythrocyte-antibody complement rosette formation, and B-cell (a-like or HLA-DR) antigens detected by a B-cell antiserum. T-cell markers included spontaneous sheep red blood cell rosette formation and a cytotoxic reaction to a specific T-cell antiserum. Seven patients with CLL and two with ALL had dual B and T markers. We propose that dual B- and T-cell markers are more common in CLL and ALL patients than previously reported. With newer and more sensitive tests for identification of B and T cells, this observation may be recognized more frequently.

scholarly journals Dual B and T markers in acute and chronic lymphocytic leukemia

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 16-20 ◽  
Author(s):  
KA Foon ◽  
RJ Billing ◽  
PI Terasaki
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Surface Membrane ◽  
Lymphocytic Leukemia ◽  
Rosette Formation ◽  
Leukemic Cells ◽  
Cell Markers ◽  
Membrane Immunoglobulin

Abstract Leukemic cells from 20 patients with chronic lymphocytic leukemia (CLL) and 60 patients with acute lymphocytic leukemia (ALL) were studied for T- and B-lymphocyte cell surface membrane markers. B-cell markers included surface membrane immunoglobulin, erythrocyte-antibody complement rosette formation, and B-cell (a-like or HLA-DR) antigens detected by a B-cell antiserum. T-cell markers included spontaneous sheep red blood cell rosette formation and a cytotoxic reaction to a specific T-cell antiserum. Seven patients with CLL and two with ALL had dual B and T markers. We propose that dual B- and T-cell markers are more common in CLL and ALL patients than previously reported. With newer and more sensitive tests for identification of B and T cells, this observation may be recognized more frequently.

scholarly journals Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions

2020 ◽  
Vol 21 (5) ◽  
pp. 1825 ◽  
Author(s):  
Francesca Arruga ◽  
Benjamin Baffour Gyau ◽  
Andrea Iannello ◽  
Nicoletta Vitale ◽  
Tiziana Vaisitti ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Molecular Mechanisms ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Adaptive Immune

Representing the major cause of morbidity and mortality for chronic lymphocytic leukemia (CLL) patients, immunosuppression is a common feature of the disease. Effectors of the innate and the adaptive immune response show marked dysfunction and skewing towards the generation of a tolerant environment that favors disease expansion. Major deregulations are found in the T lymphocyte compartment, with inhibition of CD8+ cytotoxic and CD4+ activated effector T cells, replaced by exhausted and more tolerogenic subsets. Likewise, differentiation of monocytes towards a suppressive M2-like phenotype is induced at the expense of pro-inflammatory sub-populations. Thanks to their B-regulatory phenotype, leukemic cells play a central role in driving immunosuppression, progressively inhibiting immune responses. A number of signaling cascades triggered by soluble mediators and cell–cell contacts contribute to immunomodulation in CLL, fostered also by local environmental conditions, such as hypoxia and derived metabolic acidosis. Specifically, molecular pathways modulating T-cell activity in CLL, spanning from the best known cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death 1 (PD-1) to the emerging T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)/CD155 axes, are attracting increasing research interest and therapeutic relevance also in the CLL field. On the other hand, in the microenvironment, the B cell receptor (BCR), which is undoubtedly the master regulator of leukemic cell behavior, plays an important role in orchestrating immune responses, as well. Lastly, local conditions of hypoxia, typical of the lymphoid niche, have major effects both on CLL cells and on non-leukemic immune cells, partly mediated through adenosine signaling, for which novel specific inhibitors are currently under development. In summary, this review will provide an overview of the molecular and microenvironmental mechanisms that modify innate and adaptive immune responses of CLL patients, focusing attention on those that may have therapeutic implications.

Identification of Novel Tumor-Associated Antigens in Chronic Lymphocytic Leukemia (CLL) by Serological Proteome Analysis (SERPA)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3878-3878
Author(s):  
Marta Coscia ◽  
Valentina Griggio ◽  
Michela Capello ◽  
Candida Vitale ◽  
Federica Linty ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Proteome Analysis ◽  
Lymphocytic Leukemia ◽  
Tumor Associated Antigens ◽  
Peptide Mass ◽  
Mutational Status ◽  
Pulsed Dc

Abstract Abstract 3878 Introduction: In this study, a serological proteome analysis (SERPA) was applied for the first time to identify novel tumor-associated antigens (Ags) capable of eliciting humoral immune responses in patients with chronic lymphocytic leukemia (CLL). SERPA has been demonstrated to be a valuable method to identify tumor associated Ags in several human solid and hematological malignancies. The identification and characterization of circulating antibodies (Abs) and corresponding Ags in CLL can provide useful information to understand cell transformation, predict clinical outcome, and develop immune-based interventions. Methods: SERPA was performed in 21 untreated patients. Proteins extracted from purified CLL cells were separated by 2-D electrophoresis (2-DE) to obtain proteomic maps which were blotted with corresponding sera by Western Blot to reveal Ab-based reactivity with autologous proteins. To verify the CLL specificity of Abs recognition, 7 out of 21 maps were also probed with sera collected from 7 healthy donors (HD). For identification, Ag spots in WB were aligned with proteins in 2-DE maps. The protein spots corresponding to the assigned Ags were excised from the gel, trypsin digested and analyzed by peptide mass fingerprint by MALDITOF Mass Spectrometry (MS) with the software MASCOT. T cells from 6 CLL patients and 3 HD were stimulated with autologous ENOA-pulsed and control dendritic cells (DC) and evaluated by IFNγ ELISPOT assay. Ags surface expression was analyzed by flow cytometry. Statistical correlations were performed using t-test, Mann-Withney rank sum test and χ2-test. Results: Sixteen out of 21 CLL sera (76%) were immunoreactive and produced a total number of 45 Ag spots, whereas HD sera produced only 3 spots (p<.03). Eleven out of 16 (69%) reactive CLL sera recognized from 2 to 6 different Ags in each individual patients. MS analyses led to the identification of 16 different Ags and many of them were recognized by sera from different patients. Forty-eight percent of CLL sera reacted against α-Enolase (ENOA), whereas none of HD sera was ENOA reactive. The IGHV mutational status was available in 19 CLL patients: 10 were mutated (M), while 9 were unmutated (UM). Interestingly, ENOA was recognized by sera from 7/10 M patients (70%), but only by sera from 3/9 UM patients (33%). Cytofluoroimetric analyses performed in 7 patients showed that ENOA was undetectable on viable CLL cells surface, whereas it was translocated on the membrane of apoptotic CLL cells. Statistical correlation analyses showed that immunoreactive CLL patients are characterized by an early stage of disease. Moreover, ENOA-reactive patients have a better preserved immune system because they have higher numbers of CD3+ (p=.02), CD3+/CD4+ (p=.03) and CD3+/CD8+ (p=.05) cells in the peripheral blood than ENOA-unreactive patients. We also investigated the possibility to induce ENOA-specific T-cell immune responses in 6 CLL patients. ENOA-pulsed DC induced IFNγ production in 4/6 patients (66%). The response was ENOA and CLL specific because: 1) it was not induced by unpulsed DC or DC pulsed with an irrelevant protein; 2) it was not induced when T cells from 3 HD were stimulated with autologous ENOA-pulsed DC. Interestingly, ENOA Abs were detectable by SERPA in 3 out of 4 (75%) patients with ENOA-induced T-cell responses, whereas they were undetectable in patients with unresponsive T cells. Correlations with the IGHV mutational status showed that all patients with ENOA-reactive T cells were M. Conclusions: These results indicate that ENOA is able to elicit specific humoral and cellular immune responses suggesting that this protein can be a promising biomarker and a potential target for immunotherapy in CLL. Disclosures: Massaia: Novartis Farma S.p.A: Honoraria, Research Funding.

scholarly journals T Cell Defects and Immunotherapy in Chronic Lymphocytic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3255
Author(s):  
Elisavet Vlachonikola ◽  
Kostas Stamatopoulos ◽  
Anastasia Chatzidimitriou
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
B Lymphocytes ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Lymphocytic Leukemia ◽  
Cell Compartment ◽  
The Past ◽  
Great Dependency

In the past few years, independent studies have highlighted the relevance of the tumor microenvironment (TME) in cancer, revealing a great variety of TME-related predictive markers, as well as identifying novel therapeutic targets in the TME. Cancer immunotherapy targets different components of the immune system and the TME at large in order to reinforce effector mechanisms or relieve inhibitory and suppressive signaling. Currently, it constitutes a clinically validated treatment for many cancers, including chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes with great dependency on microenvironmental signals. Although immunotherapy represents a promising therapeutic option with encouraging results in CLL, the dysfunctional T cell compartment remains a major obstacle in such approaches. In the scope of this review, we outline the current immunotherapeutic treatment options in CLL in the light of recent immunogenetic and functional evidence of T cell impairment. We also highlight possible approaches for overcoming T cell defects and invigorating potent anti-tumor immune responses that would enhance the efficacy of immunotherapy.

scholarly journals HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL)

2014 ◽  
Vol 112 (2) ◽  
pp. E166-E175 ◽  
Author(s):  
Daniel J. Kowalewski ◽  
Heiko Schuster ◽  
Linus Backert ◽  
Claudia Berlin ◽  
Stefan Kahn ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Hla Class I ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Immune Recognition ◽  
Hla Ligandome

The breakthrough development of clinically effective immune checkpoint inhibitors illustrates the potential of T-cell–based immunotherapy to effectively treat malignancies. A remaining challenge is to increase and guide the specificities of anticancer immune responses, e.g., by therapeutic vaccination or by adoptive T-cell transfer. By analyzing the landscape of naturally presented HLA class I and II ligands of primary chronic lymphocytic leukemia (CLL), we delineated a novel category of tumor-associated T-cell antigens based on their exclusive and frequent representation in the HLA ligandome of leukemic cells. These antigens were validated across different stages and mutational subtypes of CLL and found to be robustly represented in HLA ligandomes of patients undergoing standard chemo-/immunotherapy. We demonstrate specific immune recognition of these antigens exclusively in CLL patients, with the frequencies of representation in CLL ligandomes correlating with the frequencies of immune recognition by patient T cells. Moreover, retrospective survival analysis revealed survival benefits for patients displaying immune responses to these antigens. These results directly imply these nonmutant self-peptides as pathophysiologically relevant tumor antigens and encourages their implementation for cancer immunotherapy.

T-cell responses against chronic lymphocytic leukemia cells: implications for immunotherapy

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Angela M. Krackhardt ◽  
Sabine Harig ◽  
Mathias Witzens ◽  
Ryan Broderick ◽  
Patrick Barrett ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Cytotoxic T Cells ◽  
Lymphocytic Leukemia ◽  
Cell Responses ◽  
Healthy Donors ◽  
T Cell Lines ◽  
Antigen Presenting

Abstract Chronic lymphocytic leukemia (CLL) cells are ineffective antigen-presenting cells (APCs) although CD40-activated CLL cells can stimulate proliferation of autologous and allogeneic T cells. We examined the antigen-presenting capacity of CD40-activated CLL cells as well as dendritic cells pulsed with apoptotic bodies of CLL cells to generate autologous and allogeneic immune responses against CLL cells. Both APC types were capable of generating T-cell lines that proliferate specifically in response to unstimulated CLL cells. Whereas cytotoxic responses against stimulated and unstimulated CLL cells could be repeatedly generated by allogeneic healthy donors, autologous cytotoxic immune responses against CD40-activated and native CLL cells were rarely detected. However, T cells isolated from patients with CLL could recognize and lyse allogeneic stimulated and unstimulated CLL cells, demonstrating that cytotoxic T cells from these tumor-bearing patients are functionally intact.

Sign in / Sign up

Export Citation Format

Share Document