T-cell receptor repertoire of cytomegalovirus-specific cytotoxic T-cells after allogeneic stem cell transplantation

Toya, Takashi; Taguchi, Ayumi; Kitaura, Kazutaka; Misumi, Fumi; Nakajima, Yoshiyuki; Otsuka, Yuki; Konuma, Ryosuke; Adachi, Hiroto; Wada, Atsushi; Kishida, Yuya; Konishi, Tatsuya; Nagata, Akihito; Yamada, Yuta; Marumo, Atsushi; Noguchi, Yuma; Yoshifuji, Kota; Mukae, Junichi; Inamoto, Kyoko; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Ohashi, Kazuteru; Suzuki, Ryuji; Nagamatsu, Takeshi

doi:10.1038/s41598-020-79363-2

Cited by 7 publications

(4 citation statements)

References 61 publications

(80 reference statements)

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“…To document the impact of allogeneic HLA class I molecules on the modulation of KIR2DL3 + T cell function and in absence of well-established leukemia model, we focused our investigations on HLA-A2-pp65 specific T lymphocytes. Indeed, KIR expression has been previously documented on these cells in allogeneic HSCT patients 31 , 42 . HLA-C*04:01 encoded molecule belongs to C2 group of KIR ligands.…”

Section: Discussionmentioning

confidence: 93%

Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

David

Willem

Legrand

et al. 2021

Sci Rep

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KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investigation of NK receptors on T lymphocytes during immune reconstitution after T-cell-replete haploidentical HSCT with Post-Transplant Cyclophosphamide (PTCy) has shown a significant increase of KIR2DL2/3+ T cell frequency at day 25. This was especially observed at day 30 in recipients who relapsed. IL-15 but not IL-12 increased in vitro KIR+ T cell expansion suggesting that the raised IL-15 serum concentration observed after PTCy in haploidentical HSCT might increase KIR+ T cell frequency. Moreover, investigations from healthy blood donors showed a higher inhibiting effect of KIR2DL3 on CMV specific T cell response against allogeneic than autologous C1+ target cells. The association of KIR+ T cell subset with relapse may suggest that inhibitory KIR2DL2/3 limit anti-leukemic effect of specific T lymphocytes at this early step of immune reconstitution. Further phenotypic and mechanistic investigations on this cell subset from a broader cohort of HSCT recipients should clarify its potential implication in relapse occurrence. Our results demonstrate that KIR-HLA interactions known to modulate NK cell functions also modulate T cell immune responses in the context of allogeneic HSCT.

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Section: Discussionmentioning

confidence: 93%

Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

David

Willem

Legrand

et al. 2021

Sci Rep

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“…These results might reflect impaired immunity in the recipients. However, CMV reactivation is associated with modified immunity [25][26][27][28] and variable infections. [29][30][31] In addition,…”

Section: Discussionmentioning

confidence: 99%

“…These results might reflect impaired immunity in the recipients. However, CMV reactivation is associated with modified immunity 25–28 and variable infections 29–31 . In addition, CMV reactivation has been reported to be associated with a poor response after vaccination against hepatitis B virus in SCT recipients 32 .…”

Section: Discussionmentioning

confidence: 99%

Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

et al. 2022

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Antibody persistence several months after SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients remains largely unknown. We sequentially evaluated the humoral response to two doses of mRNA vaccines in 128 adult recipients and identified the risk factors involved in a poor response. The median interval between stem cell transplantation and vaccination was 2.7 years. The SARS‐CoV‐2 S1 antibody became positive after the second vaccination dose in 87.6% of the recipients, and the median titer was 1,235.4 arbitrary units (AU)/mL. In patients on corticosteroid treatment, the corticosteroid dose inversely correlated with antibody titer. Multivariate analysis identified risk factors for poor peak response such as an interval from stem cell transplantation ≤ 1 year, history of clinically significant cytomegalovirus infection, and use of > 5 mg/day prednisolone at vaccination. Six months after vaccination, the median titer decreased to 185.15 AU/mL, and use of > 5 mg/day prednisolone at vaccination was significantly associated with a poor response. These results indicate that early vaccination after stem cell transplantation (<12 months) and cytomegalovirus infection are risk factors for poor peak response, while steroid use is important for a peak as well as a persistent response. In conclusion, although humoral response is observed in many stem cell transplantation recipients after two doses of vaccination, antibody titers diminish with time, and factors associated with persistence and a peak immunity should be considered separately.

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“…Besides chimeric antigen receptor (CAR) transduction, T lymphocytes can also be genetically engineered with αβ T cell receptor expression, which is capable of recognizing MHC-restricted peptide antigens and therefore poised to turn into an important pillar of cellular cancer immunotherapy [82,111]. Generally, TCRs are capable of recognizing a relatively broad range of human leucocyte antigen (HLA)/ specific peptide that can be expressed in the surface of patient's T cells [112][113][114]. Therefore, TCR-Ts hold the potential to redirect the recognition of tumor-associated surface antigens and the removal of cancer cells.…”

Section: T Cell Receptor-engineered T Cells (Tcr-ts)mentioning

confidence: 99%

Cancer Immunotherapy and Cytotoxicity: Current Advances and Challenges

Zhang¹,

Cai²

2023

Cytotoxicity - Understanding Cellular Damage and Response

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Immunotherapies are revolutionizing strategies for cancer treatment and infectious disease administration, which thus occupy worldwide concerns and enthusiasms for conquering relapsing and refractory immunodysfuction-related diseases. Current preclinical and clinical studies have suggested the partial success and promising potential of cancer management by various immunotherapies such as cancer vaccine, lymphocyte-promoting cytokines, checkpoint inhibitors and the cellular immunotherapy. However, the precise controlled modulation of the recipient’s immune system as well as the concomitant cytotoxicity remains the core challenge in the broad implementation of cancer immunotherapies. In this Chapter, we mainly focus on the latest updates of the cytotoxicity of cancer immunocytotherapy, together with the remarkable opportunities and conspicuous challenges, which represent the paradigm for boosting the immune system to enhance antitumor responses and ultimately eliminate malignancies. Collectively, we summarize and highlight the auspicious improvement in the efficacy and cytotoxicity of cancer immunotherapy and will benefit the large-scale preclinical investigations and clinical practice in adoptive immunotherapy.

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T-cell receptor repertoire of cytomegalovirus-specific cytotoxic T-cells after allogeneic stem cell transplantation

Cited by 7 publications

References 61 publications

Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

Cancer Immunotherapy and Cytotoxicity: Current Advances and Challenges

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