scholarly journals Human Papillomavirus Type 33 E7 Peptides Presented by HLA-DR*0402 to Tumor-Infiltrating T Cells in Cervical Cancer

2000 ◽  
Vol 74 (14) ◽  
pp. 6632-6636 ◽  
Author(s):  
Hanni Höhn ◽  
Henryk Pilch ◽  
Susanne Günzel ◽  
Claudia Neukirch ◽  
Kirsten Freitag ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Peripheral Blood Lymphocytes ◽  
Tumor Rejection ◽  
Autologous Tumor ◽  
Hla Dr

ABSTRACT Several characteristics make human papillomavirus (HPV) amenable to vaccination. Anti-HPV-directed vaccines are based on the observation that HPV E6 and E7 oncoproteins are constitutively expressed in HPV-positive cervical cancer and may serve as tumor rejection antigens. Five HPV types (16, 18, 31, 33, and 45) account for 80% of cervical cancer. Until now, the type of immune response capable of mediating an effective antitumor response has not been defined. In order to define the anticancer-directed immune response in situ, we characterized CD4+ and CD8+ sorted T cells from peripheral blood lymphocytes, freshly harvested tumor tissue, and tumor-infiltrating lymphocytes (TIL) from a patient with cervical cancer. The HLA-DR-restricted CD4+ T-cell receptor VB16-, VA10-, VA21-, and VA22-positive CD4+ T-cell line derived from TIL recognizes autologous HLA-DR*0402+(HPV33+) cervical cancer cells, as determined by gamma interferon secretion. Testing of different peptides spanning the E7 gene revealed that the HPV3373–87 peptide ASDLRTIQQLLMGTV represents the immunodominant epitope which can also be presented by the DR*0401 allele to TIL. Such major histocompatibility complex class II-presented peptides represent attractive candidates to augment T-cell responses directed against autologous tumor cells.

scholarly journals Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein

2003 ◽  
Vol 77 (9) ◽  
pp. 5464-5474 ◽  
Author(s):  
Katja Nilges ◽  
Hanni Höhn ◽  
Henryk Pilch ◽  
Claudia Neukirch ◽  
Kirsten Freitag ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
Antiviral Immune Response ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses

ABSTRACT Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+ T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8+-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E711-19(20) and coronavirus NS252-60 represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed ≥0.1% HPV16 E7-reactive T cells in CD8+ peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E711-19(20) CD8+-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.

scholarly journals Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

2021 ◽  
Author(s):  
Marion Moreews ◽  
Kenz Le Gouge ◽  
Alicia Bellomo ◽  
Christophe Malcus ◽  
Rémi Pescarmona ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Kawasaki Disease ◽  
T Cell Activation ◽  
Toxic Shock Syndrome ◽  
Healthy Children ◽  
Toxic Shock ◽  
Hla Dr ◽  
Inflammatory Syndrome

AbstractObjectivesMultiple Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of COVID-19 and occurs in previously healthy children. MIS-C combines features of Kawasaki disease and Toxic Shock Syndrome (TSS).MethodsChildren with suspected MIS-C were included within the first week of diagnosis and a large scale immunoassay was performed to determein the immunologic signature of these patients.ResultsWe characterized the immunological profile of 27 MIS-C cases in comparison with 4 KD and 4 TSS cases. Similarly to TSS, an increase of serum inflammatory cytokines (IL-6, TNF-a, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR monocytes, a feature often associated with immune paralysis. Expansions of T cells expressing the Vβ21.3 T cell receptor β chain variable region were detected in both CD4 and CD8 subsets in almost 50% of patients and Vβ21.3-positive T cells expressed high level of HLA-DR highlighting their specific activation. TCR sequencing uncovered the polyclonal nature of the Vβ 21.3+ population. SARS-CoV2 antigene-specific production of interferon gamma in T cells was not increased in MIS-C T cells compared to COVID-19 patients suggesting the antigen-specific immune response in MIS-C patients is not pivotal to the manifestation.ConclusionsOur findings argue in favor of a strong activation of the immune system related to a superantigenic immune response in MIS-C with a specific polyclonal Vβ21.3 T cell expansion.Key messagesWhat is already known about this subject ?MIS-C occurs 3-5 weeks after acute SARS-CoV2 infection and overlap features of Toxic Shock syndrome and Kawasaki disease.MIS-C appears different in term of cytokine and autoantibodies generation from KD with subtle signs of T cells activationWhat does this study add?This study demonstrates that Vβ21.3+ CD4 and CD8 T cells are highly increased in about 50% of MIS-C and distinctive of the Vβ2+ expansion observed in toxic shock syndrome in This reflects a specific T cell activation and cytokine release syndrome similar to toxic shock syndromeHow mich this impact on clinical practice or future developments?Vβ21.3+ signature can be available on a short term basis by flowcytometry and represents a signature of the MIS-C.As for TSS, immunomodulating therapies may revert the superantigenic activation and resolve this life threatening pediatric condition.

scholarly journals The Polyomavirus BK Large T-Antigen-Derived Peptide Elicits an HLA-DR Promiscuous and Polyfunctional CD4+T-Cell Response

2011 ◽  
Vol 18 (5) ◽  
pp. 815-824 ◽  
Author(s):  
Bala Ramaswami ◽  
Iulia Popescu ◽  
Camila Macedo ◽  
Chunqing Luo ◽  
Ron Shapiro ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Antigen ◽  
T Cell Response ◽  
Peptide Sequence ◽  
Large T Antigen ◽  
Hla Dr ◽  
Ifn Γ

ABSTRACTBK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4+T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4+T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.

scholarly journals Qualitative Analysis of Tumor-Infiltrating Lymphocytes across Human Tumor Types Reveals a Higher Proportion of Bystander CD8+ T Cells in Non-Melanoma Cancers Compared to Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3344
Author(s):  
Aishwarya Gokuldass ◽  
Arianna Draghi ◽  
Krisztian Papp ◽  
Troels Holz Borch ◽  
Morten Nielsen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Autologous Tumor ◽  
Epithelial Cancers ◽  
Single Cell Rna Sequencing ◽  
Tumor Types ◽  
Infiltrating Lymphocytes

Background: Human intratumoral T cell infiltrates can be defined by quantitative or qualitative features, such as their ability to recognize autologous tumor antigens. In this study, we reproduced the tumor-T cell interactions of individual patients to determine and compared the qualitative characteristics of intratumoral T cell infiltrates across multiple tumor types. Methods: We employed 187 pairs of unselected tumor-infiltrating lymphocytes (TILs) and autologous tumor cells from patients with melanoma, renal-, ovarian-cancer or sarcoma, and single-cell RNA sequencing data from a pooled cohort of 93 patients with melanoma or epithelial cancers. Measures of TIL quality including the proportion of tumor-reactive CD8+ and CD4+ TILs, and TIL response polyfunctionality were determined. Results: Tumor-specific CD8+ and CD4+ TIL responses were detected in over half of the patients in vitro, and greater CD8+ TIL responses were observed in melanoma, regardless of previous anti-PD-1 treatment, compared to renal cancer, ovarian cancer and sarcoma. The proportion of tumor-reactive CD4+ TILs was on average lower and the differences less pronounced across tumor types. Overall, the proportion of tumor-reactive TILs in vitro was remarkably low, implying a high fraction of TILs to be bystanders, and highly variable within the same tumor type. In situ analyses, based on eight single-cell RNA-sequencing datasets encompassing melanoma and five epithelial cancers types, corroborated the results obtained in vitro. Strikingly, no strong correlation between the proportion of CD8+ and CD4+ tumor-reactive TILs was detected, suggesting the accumulation of these responses in the tumor microenvironment to follow non-overlapping biological pathways. Additionally, no strong correlation between TIL responses and tumor mutational burden (TMB) in melanoma was observed, indicating that TMB was not a major driving force of response. No substantial differences in polyfunctionality across tumor types were observed. Conclusions: These analyses shed light on the functional features defining the quality of TIL infiltrates in cancer. A significant proportion of TILs across tumor types, especially non-melanoma, are bystander T cells. These results highlight the need to develop strategies focused on the tumor-reactive TIL subpopulation.

Leukemic Blasts Acting as Host Antigen Presenting Cells Trigger a Combined CD4 and CD8 Allo-Immune Response Directed Against Mismatched HLA Class I.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5030-5030
Author(s):  
Avital Amir ◽  
Renate S. Hagendoorn ◽  
Erik W.A. Marijt ◽  
Roelof Willemze ◽  
J.H. Frederik Falkenburg ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Hla Class I ◽  
Cd8 T Cell ◽  
Class I ◽  
Mixed Chimerism ◽  
Target Cells ◽  
Hla Dr ◽  
Donor T Cells

Abstract Single HLA locus mismatched stem cell transplantation (SCT) is applied in patients with hematological malignancies who may benefit from allogeneic transplantation but lack an HLA-matched donor. Although HLA disparity between patient and donor increases the risk of developing GVHD, the relative risk of GVHD after single HLA locus mismatched SCT is only 1.5 fold. In view of the high frequency of allo-HLA reactive T-cells, which is about 1000-fold higher than the frequencies of minor histocompatibility antigen specific T-cells, this risk increase is lower than could be expected. Since almost all nucleated cells express HLA class I, one would expect all single HLA class I mismatched transplanted patients to develop severe GVHD. We hypothesized therefore that the presentation of the HLA class I mismatched allele on nucleated cells of the patient is not sufficient to elicit an effective allo-immune response. We characterized the allo-immune response in a patient with acute myeloid leukemia (AML) who was treated with a T-cell depleted SCT from a sibling donor who was HLA identical except for an HLA-A2 crossover. Six months after SCT, donor lymphocyte infusion (DLI) of 2.5*10e6 T-cells/kg was given for mixed chimerism comprising 99% T-cells of patient origin. No clinical response and no GVHD developed. Twelve months after SCT 95% of T-cells were still of patient origin, and AML relapse occurred with 9% blasts in bone marrow for which a second DLI containing 7.5*10e6 T-cells/kg was given. Five weeks after the DLI the patient died of grade IV GVHD. During the GVHD, conversion to donor chimerism developed. In peripheral blood of the patient 90% of CD8 and 40% of CD4 donor T-cells were activated as determined by HLA-DR expression. To analyze the nature of the immune response, the activated CD8 and CD4 donor T-cells were single cell sorted, expanded and tested for alloreactivity and HLA restriction using cytotoxicity and cytokine production assays against a panel of target cells blocked with different HLA-mAbs. 82% of the CD8 T-cell clones were alloreactive and restricted to the allo-HLA-A2. The response was highly polyclonal as shown by the usage of different T-cell receptor Vβ chains with different CDR3 sequences. 26% of the CD4 clones were alloreactive and this response was also polyclonal. The CD4 clones were HLA-DR1 restricted and recognized donor EBV-LCL transduced with HLA-A2, indicating that the peptide recognized in HLA-DR1 was derived from the mismatched HLA-A2 molecule. The recognized epitope was demonstrated to comprise AA 103–120 derived from a hypervariable region of HLA-A2. At the time of the first DLI, only HLA class I expressing T-cells and non-hematopoietic patient derived cells were present, capable of activating the CD8 T-cells but not of triggering the CD4 response. Leukemic blasts present at the time of the second DLI, however, expressed both HLA-DR and HLA class I, and were shown to activate the CD4 as well as the CD8 clones. We hypothesize that the HLA class II expression on hematopoietic cells of the patient at the time of the relapse was essential for the development of this immune response. In conclusion, these results indicate a role for patient leukemic blasts acting as host APCs in initiating the GVH response by activating both a CD4 and CD8 T-cell response in an HLA class I mismatched setting.

scholarly journals The mutational load and a T-cell inflamed tumor phenotype identify ovarian cancer patients rendering tumor-reactive T cells from PD-1+ tumor-infiltrating lymphocytes

2020 ◽  
Author(s):  
Diego Salas-Benito ◽  
Enrique Conde ◽  
Ibon Tamayo-Uria ◽  
Uxua Mancheño ◽  
Edurne Elizalde ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
T Cell ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
Ovarian Tumors ◽  
Autologous Tumor ◽  
Tumor Mutational Burden ◽  
Nanostring Technology ◽  
Infiltrating Lymphocytes

Abstract Background: Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as programmed cell death protein 1 (PD-1), for tumor-specific T-cell enrichment, as well as predictive biomarkers that help identify those patients capable of rendering tumor-reactive TIL products. We have investigated this in ovarian cancer (OC) patients as candidate for TIL therapy implementation. Methods: PD-1- and PD-1+ CD8 TILs were isolated from resected ovarian tumors and, after polyclonal expansion, TIL products were tested against autologous tumor cells. Reactivity was assessed by IFNg production (ELISPOT) and upregulation of CD137. Baseline tumor samples were examined using flow cytometry, multiplexed quantitative immunofluorescence, Nanostring technology, for gene expression profile (GEP) analyses, as well as a next generation sequencing gene panel, for tumor mutational burden (TMB) calculation, to identify those features that distinguished patients with tumor-reactive and non-tumor-reactive TIL products.Results: Tumor-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction. Flow-cytometric studies revealed that fresh tumors from patients rendering tumor-reactive TILs presented a significantly higher frequency of CD137+ cells within the PD1+CD8+ subset. Multiplexed immunofluorescence supported this finding, which was particularly striking in intraepithelial CD8 TILs. Baseline GEP analysis showed that patients rendering tumor-reactive TILs exhibited a significantly higher T-cell inflamed signature. Despite no correlation between TMB and GEP, both parameters stratified tumors, with patients with higher TMB and/or T-cell inflamed signature score rendering tumor-reactive TILs. Conclusion: We have demonstrated that PD-1 identifies autologous-tumor specific CD8 T cells infiltrating ovarian tumors and have uncovered predictive factors that identify OC patients who are likely to render tumor-reactive cells from PD-1+ TILs. These findings have important implications for improving the efficacy of TIL therapy in OC.

scholarly journals S-15 in combination of Akt inhibitor promotes the expansion of CD45RA−CCR7+ tumor infiltrating lymphocytes with high cytotoxic potential and downregulating PD-1+Tim-3+ cells as well as regulatory T cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Benling Xu ◽  
Long Yuan ◽  
Guangyu Chen ◽  
Tiepeng Li ◽  
Jinxue Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Hepatocellular Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
T Cell Differentiation ◽  
Great Promise ◽  
Autologous Tumor ◽  
Akt Inhibitor ◽  
Infiltrating Lymphocytes

Abstract Background Autologous tumor-infiltrating lymphocytes (Tils) immunotherapy is a promising treatment in patients with advanced hepatocellular cancer. Although Tils treatment has shown great promise, their persistence and the efficacy after adoptive-transfer are insufficient and remain a challenge. Studies have demonstrated that IL-15 and Akt inhibitor can regulate T cell differentiation and memory. Here, we constructed S-15 (Super human IL-15), a fusion protein consisting of human IL-15, the sushi domain of the IL-15 receptor α chain and human IgG-Fc. Herein we compared the effects of S-15 with IL-2 or in combination with Akti on the expansion and activation of Tils. Methods Hepatocellular cancer tissues were obtained from 6 patients, Tils were expanded using IL-2, IL-2/S-15, IL-2/Akti or in combination IL-2/S-15/Akti. At day 10, anti-CD3 antibody was added to the culture media and expanded to day 25. The composition, exhaustion and T-cell differentiation markers (CD45RA/CCR7) were analyzed by flow cytometry. Results We found that IL-2/S-15/Akti expanded Tils and showed the highest percentage of central memory CD45RA−CCR7+ phenotype prior to anti-CD3 antibody activation and after anti-CD3 antibody activation. T cells cultured with IL-2/S-15/Akti exhibited a mixture of CD4+, CD8+, and CD3+CD4−CD8− T cells; S-15 in combination with Akt inhibitor downregulated the expression of PD-1+Tim-3+ on Tils and decreased the Tregs in Tils. Additionally, the Tils expanded in the presence of the Akt inhibitor and S-15 showed enhanced antitumor activity as indicated by the increase in IFN-γ producing tumor infiltrating CD8+ T cells and without comprising the Tils expansion. Conclusion Our study elucidates that IL-2/S-15/Akti expanded Tils and represent a viable source for the cellular therapy for patients with hepatocellular cancer.

scholarly journals Combinatorial immunotherapy induces tumor-infiltrating CD8+ T cells with distinct functional, migratory, and stem-like properties

2021 ◽  
Vol 9 (12) ◽  
pp. e003614
Author(s):  
Natalija Van Braeckel-Budimir ◽  
Joseph Samuel Dolina ◽  
Jie Wei ◽  
Xiao Wang ◽  
Shih-Hsun Chen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Agent ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoint Blockade ◽  
Tumor Rejection ◽  
Cell Subpopulation ◽  
Ki 67 ◽  
Combinatorial Immunotherapy ◽  
Infiltrating Lymphocytes

BackgroundProgrammed death (ligand) 1 (PD-(L)1) blockade and OX40/4-1BB costimulation have been separately evaluated in the clinic to elicit potent antitumor T cell responses. The precise mechanisms underlying single agent activity are incompletely understood. It also remains unclear if combining individual therapies leads to synergism, elicits novel immune mechanisms, or invokes additive effects.MethodsWe performed high-dimensional flow cytometry and single-cell RNA sequencing-based immunoprofiling of murine tumor-infiltrating lymphocytes (TILs) isolated from hosts bearing B16 or MC38 syngeneic tumors. This baseline infiltrate was compared to TILs after treatment with either anti-PD-(L)1, anti-OX40, or anti-4-1BB as single agents or as double and triple combinatorial therapies. Fingolimod treatment and CXCR3 blockade were used to evaluate the contribution of intratumoral versus peripheral CD8+ T cells to therapeutic efficacy.ResultsWe identified CD8+ T cell subtypes with distinct functional and migratory signatures highly predictive of tumor rejection upon treatment with single agent versus combination therapies. Rather than reinvigorating terminally exhausted CD8+ T cells, OX40/4-1BB agonism expanded a stem-like PD-1loKLRG-1+Ki-67+CD8+ T cell subpopulation, which PD-(L)1 blockade alone did not. However, PD-(L)1 blockade synergized with OX40/4-1BB costimulation by dramatically enhancing stem-like TIL presence via a CXCR3-dependent mechanism.ConclusionsOur findings provide new mechanistic insights into the interplay between components of combinatorial immunotherapy, where agonism of select costimulatory pathways seeds a pool of stem-like CD8+ T cells more responsive to immune checkpoint blockade (ICB).

scholarly journals The Effect of Cardiac Surgery on Peripheral Blood Lymphocyte Populations

2008 ◽  
Vol 51 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Karolína Jankovičová ◽  
Manuela Trojáčková Kudlová ◽  
Martina Koláčková ◽  
Pavel Kuneš ◽  
Jiří Manďák ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cardiac Surgery ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Off Pump ◽  
Hla Dr ◽  
Alternative Approach ◽  
Altered Immune Response ◽  
Lymphocyte Populations

Background: Cardiac surgery using cardiopulmonary bypass (CPB) is associated with some adverse postoperative complications caused by an altered immune response. An alternative approach to cardiac surgery, operating without the use of CPB (i.e. off-pump surgery), seems to display less adverse impacts on the immune response. Patients and Methods: Peripheral blood lymphocytes in 40 patients undergoing cardiac surgery either with CPB (“on-pump”) or without CPB (“off-pump”) were followed using flow cytometry. The samples of peripheral blood were taken at five intervals: preoperatively, after termination of the surgery, on the first, on the third and on the seventh postoperative day, respectively. Results: The most substantial changes appeared on the first postoperative day in both subgroups of patients. While the percentage of both total T cells and CD4+ T cells were decreased, the percentage of HLA-DR+ activated lymphocytes was increased. These changes were more profound in the “on-pump” subgroup compared to the “off-pump” subgroup. Conclusion: Our results may suggest that the “off-pump” surgical approach reveals less adverse impact on adaptive immune responses.

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