Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer

Bari, Shahla; Chan, Austin; Jain, Sanjay; Haider, Ahmad; Curry, Marjorie Adams; Hostler, Christopher J

doi:10.1155/2019/2989048

Cited by 17 publications

(19 citation statements)

References 20 publications

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“…The latest study including 17 HIV-positive cancer patients showed that Checkpoint inhibitors seemed like to have comparable e cacy and tolerable adverse effects,and CD4 + Tlymphocyte cell count and viral load were not affected. In this study, the only one RCC patient with stage III responded to immunal thepapy with stable disease, and had slight side effects [22].…”

Section: Discussionmentioning

confidence: 59%

Human Immunodeficiency Virus Related Renal Cell Carcinoma: a Retrospective Study of 19 Cases

Zhang

Zhu

Xue

et al. 2021

Preprint

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Purpose: We aimed to investigate basic information, clinical findings, treatments for tumor, pathology and outcomes of HIV-positive patients diagnosed renal cell carcinoma(RCC). Patients and Methods: We collected 19 patients from 2012 to 2020 who diagnosed RCC with HIV- positive. A retrospective analyze was performed on their hospitalization course and tumor related parameters, including basic information, clinical findings, HIV associated datas, pathology, treatments for tumor and outcomes.Results: In our study, patients were diagnosed RCC at the median age 51. Males took a great part(17 males,89%) in all patients, while only 2 females were diagnosed. The median CD4+ T-lymphocyte cell count was 462 cells/ul when diagnosed RCC(range from 111 cells/ul to 1536 cells/ul). 11 patients diagnosed RCC and HIV infection at the same time, who may have high viral load and low CD4+ T-lymphocyte cell count. 8 patients accepted a median HAART for 30 months(range from 11 months to 108months) prior to diagnosis of RCC. All the patients performed operations successfully, and 4 of them performed partial nephrecotomy. Only 1 patient was identified with chromophobe cell carcinoma, 1 with partially clear cell and partialy papillary carcinoma, and 17 with clear cell carcinoma. 2 of the patients with Fuhrman grade2-3 accepted cytokine therapy with IL-2 and IFN-α. 2 patients died of lung metastasis one year and six months after surgery respectively, even though 1 patient accepted full dose targeted therapy (Sorafenib) for 3 months, and one refused adjuvant therapy. The remaining 17 patients are still alive at a median follow-up of 34 months, however 1 patient live with lung and brain metastases at last follow-up of 3 years after surgery.Conclusions: RCC Patients with HIV-positive were similar to general population in terms of clinical characters, treatment measures, and pathology. RCC patients with HIV- positive seemed like to obey the same clinical practice guideline as in general population. The outcomes of HIV-positive patients with partial nephrectomy are not inferior to patients with radical nephrectomy. Further more experience in targeted therapy and immunal therapy( PD-1/ PD-L1 inhibitors) needs to be learned.

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Section: Discussionmentioning

confidence: 59%

Human Immunodeficiency Virus Related Renal Cell Carcinoma: a Retrospective Study of 19 Cases

Zhang

Zhu

Xue

et al. 2021

Preprint

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“…Moreover, PD-1 blockade has shown a synergistic effect with other latency reversing agents in several pre-clinical studies ( 8 , 13 ). However, similar to the low response rate observed for PD-1 blockade in patients with cancer, only one study confirmed that anti-PD-1 therapy appears to be useful in PLWH with cancer ( 45 ), necessitating efforts that are aimed at improving efficacy using combined regimens. This strategy was corroborated by a recent report which showed that reversal of HIV latency was achieved by blockade of multiple checkpoint receptors, PD-1, CTLA4, TIM3, and TIGIT without T cell stimulation, and this effect was significantly greater than that induced by latency reversal agents such as vorinostat and bryostatin ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Reversal of the CD8+ T-Cell Exhaustion Induced by Chronic HIV-1 Infection Through Combined Blockade of the Adenosine and PD-1 Pathways

Huang

Tang

et al. 2021

Front. Immunol.

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BackgroundTargeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8+ T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8+ T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8+ T-cell subsets in chronic HIV-1 infection remain poorly understood.MethodsThis study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8+ T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8+ T cells.ResultsThe proportions of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1+CD39+ CD8+ T cells were negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39+CD8+ T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39- counterparts. In vitro, a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8+ T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells.ConclusionIn patients with chronic HIV-1 infection there are increased frequencies of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells. In treatment naïve patients, the frequencies of PD-1+CD39+ CD8+ T cells are negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling in vitro may exert a synergistic effect in restoring CD8+ T-cell function in HIV-1-infected patients.

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“…The latest study including 17 HIV-positive cancer patients showed that checkpoint inhibitors seemed like to have comparable efficacy and tolerable adverse effects, and CD4 + T lymphocyte cell count and viral load were not affected. In this study, only one RCC patient with stage III responded to immunal therapy with stable disease and had slight side effects [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus-related renal cell carcinoma: a retrospective study of 19 cases

Zhang

Zhu

Xue

et al. 2021

Infect Agents Cancer

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Purpose We aimed to investigate basic information, clinical findings, treatments for tumor, pathology, and outcomes of HIV-positive patients diagnosed with renal cell carcinoma (RCC). Patients and methods We collected 19 patients from 2012 to 2020 who are diagnosed with RCC with HIV-positive. A retrospective analysis was performed on their hospitalization course and tumor-related parameters, including basic information, clinical findings, HIV-associated data, pathology, treatments for tumor, and outcomes. Results In our study, patients were diagnosed with RCC at the median age of 51. Males took a great part (17 males, 89%) in all patients, while only 2 females were diagnosed. The median CD4+ T lymphocyte cell count was 462 cells/μl when diagnosed with RCC (range from 111 cells/μl to 1536 cells/μl). Eleven patients diagnosed with RCC and HIV infection at the same time, who may have high viral load and low CD4+ T lymphocyte cell count. Eight patients accepted a median HAART for 30 months (range from 11 months to 108 months) prior to diagnosis of RCC. All the patients performed operations successfully, and 4 of them performed partial nephrecotomy. Only 1 patient was identified with chromophobe cell carcinoma, 1 with partially clear cell and partially papillary carcinoma, and 17 with clear cell carcinoma. Two of the patients with Fuhrman grades 2–3 accepted cytokine therapy with IL-2 and IFN-α. Two patients died of lung metastasis 1 year and 6 months after surgery respectively, even though 1 patient accepted full dose targeted therapy (sorafenib) for 3 months, and one refused adjuvant therapy. The remaining 17 patients are still alive at a median follow-up of 34 months; however, 1 patient lives with lung and brain metastases at the last follow-up of 3 years after surgery. Conclusions RCC patients with HIV-positive were similar to the general population in terms of clinical characters, treatment measures, and pathology. RCC patients with HIV-positive seemed like to obey the same clinical practice guideline as in the general population. The outcomes of HIV-positive patients with partial nephrectomy are not inferior to patients with radical nephrectomy. Furthermore, experience in targeted therapy and immunal therapy (PD-1/PD-L1 inhibitors) needs to be learned.

show abstract

Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer

Cited by 17 publications

References 20 publications

Human Immunodeficiency Virus Related Renal Cell Carcinoma: a Retrospective Study of 19 Cases

Human Immunodeficiency Virus Related Renal Cell Carcinoma: a Retrospective Study of 19 Cases

Reversal of the CD8+ T-Cell Exhaustion Induced by Chronic HIV-1 Infection Through Combined Blockade of the Adenosine and PD-1 Pathways

Human immunodeficiency virus-related renal cell carcinoma: a retrospective study of 19 cases

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