Immune checkpoint inhibitors in heart or lung transplantation: Early results from a registry initiative

Daud, Anees; Mehra, Mandeep R.; Siu, Alfonso; Johnson, Maryl R.; Perch, Michael; Budev, Marie; Zakharia, Yousef; Cheng, Richard K.; Nativi-Nicolau, José; Stehlik, Josef

doi:10.1016/j.healun.2020.02.015

Cited by 15 publications

(12 citation statements)

References 7 publications

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“…Notably, our preliminary results offer support to recent data showing that the presence of PD-L1-expressing T lymphocytes in heart transplanted biopsies is predictive of organ rejection (33), and raise the possibility that modulation of PD-1 activity could be useful in preventing graft rejection. It is worth noting that an indirect confirmation of this possibility comes from hearttransplanted recipients who developed malignancies: in these patients, immune checkpoint inhibitor-based therapies resulted in rejection (8). Generalization of our results is limited by the single center nature of our study and by the limited sample size: this limitation is nevertheless difficult to overcome because re-transplantation is a scarcely practiced procedure (less than 5% of total LTx worldwide).…”

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

“…Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific antibody, anti-HLA antibodies, and interleukins in chronic rejection and CLAD ( 5 – 7 ), but the possible role of immune checkpoint molecules expression and function in this phenomenon has not yet been analyzed. Sporadic experiences with immune checkpoint inhibitor treatments of kidney and heart transplanted patients suffering from neoplastic diseases have shown that the use of these molecules results in the rapid development of severe rejection ( 8 ). These observations underline the need to better understand the possible role of immune checkpoint molecules in transplantation, and in particular in LTx.…”

Section: Introductionmentioning

confidence: 99%

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Immune Checkpoints Expression in Chronic Lung Allograft Rejection

et al. 2021

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Chronic lung allograft dysfunction (CLAD) is the main cause of poor survival and low quality of life of lung transplanted patients. Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific as well as anti-HLA antibodies, and interleukins in CLAD, but the expression and function of immune checkpoint molecules has not yet been analyzed, especially in the two CLAD subtypes: BOS (bronchiolitis obliterans syndrome) and RAS (restrictive allograft syndrome). To shed light on this topic, we conducted an observational study on eight consecutive grafts explanted from patients who received lung re-transplantation for CLAD. The expression of a panel of immune molecules (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein) was analyzed by immunohistochemistry in these grafts and in six control lungs. Results showed that RAS compared to BOS grafts were characterized by 1) the inversion of the CD4/CD8 ratio; 2) a higher percentage of T lymphocytes expressing the PD-1, PD-L1, and CTLA4 checkpoint molecules; and 3) a significant reduction of exhausted PD-1-expressing T lymphocytes (PD-1pos/TOXpos) and of exhausted Treg (PD-1pos/FOXP3pos) T lymphocytes. Results herein, although being based on a limited number of cases, suggest a role for checkpoint molecules in the development of graft rejection and offer a possible immunological explanation for the worst prognosis of RAS. Our data, which will need to be validated in ampler cohorts of patients, raise the possibility that the evaluation of immune checkpoints during follow-up offers a prognostic advantage in monitoring the onset of rejection, and suggest that the use of compounds that modulate the function of checkpoint molecules could be evaluated in the management of chronic rejection in LTx patients.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune Checkpoints Expression in Chronic Lung Allograft Rejection

et al. 2021

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“…So far, approximately, 230 SOT recipients treated with CPI has been reported in the literature. Compared with liver and heart transplant recipients, kidney transplant recipients, despite the highest rate of rejection, have the lower mortality rate [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Section: Immunotherapymentioning

confidence: 99%

“… Response refers to tumor shrinking. Numbers in the table are extracted from the systematic review by d'Izarny‐Gargas [ 12 ] updated with published literature beyond 1 November 2019 [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. …”

Section: Immunotherapymentioning

confidence: 99%

Chemotherapy, targeted therapy and immunotherapy: Which drugs can be safely used in the solid organ transplant recipients?

Maggiore

Palmisano

Buti

et al. 2021

Transplant International

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Summary In solid organ transplant recipients, cancer is associated with worse prognosis than in the general population. Among the causes of increased cancer‐associated mortality, are the limitations in selecting the optimal anticancer regimen in solid organ transplant recipients, because of the associated risks of graft toxicity and rejection, drug‐to‐drug interactions, reduced kidney or liver function, and patient frailty and comorbid conditions. The advent of immunotherapy has generated further challenges, mainly because checkpoint inhibitors increase the risk of rejection, which may have life‐threatening consequences in recipients of life‐saving organs. In general, there are no safe or unsafe anticancer drugs. Rather, the optimal choice of the anticancer regimen results from a careful risk/benefit assessment, from the awareness of potential pharmacokinetic and pharmacodynamic drug‐to‐drug interactions, and of the risk of drug overexposure in patients with kidney or liver dysfunction. In this review, we summarize general principles that may help the oncologists and transplant physicians in the multidisciplinary management of recipients of solid organ transplantation with cancer who are candidates for chemotherapy, targeted therapy, or immunotherapy.

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Lung Cancer and Lung Transplantation

Jablonski

2023

Curr Pulmonol Rep

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Immune checkpoint inhibitors in heart or lung transplantation: Early results from a registry initiative

Cited by 15 publications

References 7 publications

Immune Checkpoints Expression in Chronic Lung Allograft Rejection

Immune Checkpoints Expression in Chronic Lung Allograft Rejection

Chemotherapy, targeted therapy and immunotherapy: Which drugs can be safely used in the solid organ transplant recipients?

Lung Cancer and Lung Transplantation

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