Checkpoint Inhibitor–Induced Rejection of a Liver Allograft: A Combination of Acute T Cell–Mediated and Antibody‐Mediated Rejection

2019 ◽  
Vol 25 (12) ◽  
pp. 1845-1848 ◽  
Author(s):  
Brian T. Lee ◽  
Brian H. Horwich ◽  
Shefali Chopra ◽  
Aaron Ahearn ◽  
Hyosun H. Han
Keyword(s):  
T Cell ◽  
Checkpoint Inhibitor ◽  
Liver Allograft ◽  
Antibody Mediated Rejection

SAT-440-Molecular fingerprint of T cell-mediated and antibody-mediated rejection after human liver transplantation

2019 ◽  
Vol 70 (1) ◽  
pp. e830
Author(s):  
Anne Höfer ◽  
Danny Jonigk ◽  
Björn Hartleben ◽  
Robert Geffers ◽  
Murielle Verboom ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Human Liver ◽  
Molecular Fingerprint ◽  
Antibody Mediated Rejection

scholarly journals Melanoma Single-Cell Biology in Experimental and Clinical Settings

2021 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Hans Binder ◽  
Maria Schmidt ◽  
Henry Loeffler-Wirth ◽  
Lena Suenke Mortensen ◽  
Manfred Kunz
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Intracellular Signaling ◽  
Cell Biology ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Checkpoint Inhibitor ◽  
Treatment Resistance ◽  
Resistance Mechanisms ◽  
Cellular Heterogeneity

Cellular heterogeneity is regarded as a major factor for treatment response and resistance in a variety of malignant tumors, including malignant melanoma. More recent developments of single-cell sequencing technology provided deeper insights into this phenomenon. Single-cell data were used to identify prognostic subtypes of melanoma tumors, with a special emphasis on immune cells and fibroblasts in the tumor microenvironment. Moreover, treatment resistance to checkpoint inhibitor therapy has been shown to be associated with a set of differentially expressed immune cell signatures unraveling new targetable intracellular signaling pathways. Characterization of T cell states under checkpoint inhibitor treatment showed that exhausted CD8+ T cell types in melanoma lesions still have a high proliferative index. Other studies identified treatment resistance mechanisms to targeted treatment against the mutated BRAF serine/threonine protein kinase including repression of the melanoma differentiation gene microphthalmia-associated transcription factor (MITF) and induction of AXL receptor tyrosine kinase. Interestingly, treatment resistance mechanisms not only included selection processes of pre-existing subclones but also transition between different states of gene expression. Taken together, single-cell technology has provided deeper insights into melanoma biology and has put forward our understanding of the role of tumor heterogeneity and transcriptional plasticity, which may impact on innovative clinical trial designs and experimental approaches.

scholarly journals Preceding T-Cell-Mediated Rejection Is Associated with the Development of Chronic Active Antibody-Mediated Rejection by de Novo Donor-Specific Antibody

Nephron ◽  
2020 ◽  
pp. 1-5
Author(s):  
Takahiro Tsuji ◽  
Sari Iwasaki ◽  
Keishi Makita ◽  
Teppei Imamoto ◽  
Naomichi Ishidate ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
De Novo ◽  
Control Group ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
The Mean ◽  
Microvascular Inflammation ◽  
Renal Allograft Loss ◽  
Allograft Loss

<b><i>Aim:</i></b> Chronic active antibody-mediated rejection (CAABMR) is an important cause of late-stage renal allograft loss. Early inflammatory events such as acute rejection and infection after transplantation are considered to be the risk factors of de novo donor-specific antibody (dnDSA) production. In this study, we investigated the relationship between pre­disposing T-cell-mediated rejection and dnDSA-positive CAABMR. <b><i>Methods:</i></b> We recruited 365 patients who underwent ABO-compatible renal transplantation at our hospital. Among them, 16 patients diagnosed as having dnDSA-positive CAABMR were designated as a CAABMR group, and 38 randomly selected patients were designated as a control group. All biopsies from 1 month after transplantation were included in the study. The presence or absence of borderline changes (BLCs), acute T-cell-mediated rejection (ATMR), microvascular inflammation (MVI), and C4d positive on peritubular capillaries (C4d-P) was examined. <b><i>Results:</i></b> In the CAABMR group, BLC/ATMR was found in 12 cases (75%), and the mean duration until appearance of BLC/ATMR was 282.7 ± 328.7 days. C4d-P was found in 11 cases (68.8%), and the mean duration until its appearance was 1,432 ± 1,307 days. MVI was found in all cases, and the mean duration until its appearance was 1,333 ± 1,126 days. The mean duration until diagnosis of CAABMR was 2,268 ± 1,191 days. In the control group, BLC/ATMR was found in 13 cases (34.2%), and the mean duration until the appearance of BLC/ATMR was 173.1 ± 170.4 days. C4d-P was found in 2 cases (5.3%), and the durations until its appearance were 748 and 1,881 days. No cases of MVI were found in the control group. The frequency of BLC/ATMR was significantly higher in the CAABMR group (<i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Preceding BLC/ATMR is associated with the development of CAABMR with dnDSA.

scholarly journals Pure T-cell-mediated rejection following kidney transplant according to the response to treatment in the era of antibody-mediated rejection

2020 ◽  
Vol 34 (1) ◽  
pp. S15-S15
Author(s):  
Hyunwook Kwon ◽  
Sung Shin ◽  
Duck Jong Han ◽  
Young Hoon Kim ◽  
Joo Hee Jung ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Response To Treatment ◽  
Antibody Mediated Rejection

P1602MICROVASCULAR INFLAMMATION WITHOUT DSA OR C4D: AN ORPHAN CATEGORY IN BANFF CLASSIFICATION WITH INTENSE CAPILLARITIS AND CYTOTOXIC T-CELL INFILTRATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Buxeda ◽  
Laura Llinàs ◽  
Javier Gimeno ◽  
Carlos Arias Cabrales ◽  
Carla Burballa Tarrega ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
T Cell ◽  
Nk Cells ◽  
Lymphocyte Subsets ◽  
Normal Group ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Antibody Mediated Rejection ◽  
T Cell Infiltration ◽  
Peritubular Capillaries

Abstract Background and Aims Antibody-mediated rejection (ABMR) associated with donor-specific HLA antibodies (DSA) is the leading cause of late allograft failure after kidney transplantation. Microvascular inflammation (MVI) without detectable circulating DSA or C4d + cannot be classified as ABMR according to Banff-2017. The involvement of intragraft lymphocyte subsets in the development of humoral damage in kidney transplantation (KT) is relevant. We aimed to analyze lymphocyte subset distribution in kidney transplant biopsies (KTBx) with ABMR compared with MVI and with normal KTBx. Method KTBx with ABMR, MVI (g+ptc≥2, without DSA) or normal findings were included. DSA were identified with Luminex single antigen assays. Intragraft lymphocyte subsets’ characterization was performed by immunohistochemistry: T-lymphocytes (CD3, CD4, CD8, Foxp3), B-lymphocytes / plasmatic cells (CD20, CD138), NK cells (CD56), macrophages / monocytes (CD68), cytotoxic cells (TIA1) and activated cells (PD1) were evaluated. Results We analyzed 34 KTBx: 21 ABMR, 5 MVI and 8 KTBx with normal findings. KT with ABMR and MVI had more proteinuria at the time of the biopsy compared with the normal group (575 mg/24h and 964 mg/24h vs 147 mg/24h, p=0.002 and p=0.005 respectively). DSA were more frequently detected in patients with ABMR (95.2% vs 0% and 37.5%, p&lt;0.001 and p=0.003 respectively). KTBx with ABMR and MVI had increased cytotoxic T-cell infiltration apparently corresponding to NK cells in peritubular capillaries (ptc) compared to normal group. Moreover, both groups showed a greater number of macrophages and monocytes in glomeruli. KT with MVI but not with ABMR had a significantly increased activated cell infiltration (PD1+) in ptc compared to the normal group, and showed an increased cytotoxic T-cell infiltration in glomeruli compared to ABMR and normal groups. Conclusion ABMR and MVI have an increased infiltration of NK cells with cytotoxic activity in ptc that differs from the normal group. However, KT with MVI show greater infiltration of activated cells in ptc and cytotoxic T-cell in glomeruli compared to ABMR suggesting the possibility of different activation pathways.

scholarly journals A Review of T-Cell Related Therapy for Osteosarcoma

2020 ◽  
Vol 21 (14) ◽  
pp. 4877
Author(s):  
Kazushige Yoshida ◽  
Masanori Okamoto ◽  
Kaoru Aoki ◽  
Jun Takahashi ◽  
Naoto Saito
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Malignant Tumors ◽  
Checkpoint Inhibitor ◽  
T Cell Response ◽  
The Other ◽  
T Cell Therapy ◽  
Tumors Of Bone ◽  
Better Than

Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.

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