Programmed death-1 expression is associated with the disease status in hepatitis B virus infection

AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen specific CD8＋T cells in peripheral blood of patients with chronic hepatitis B （CriB） and acute exacerbation of hepatitis B （AEHB） infection. METHODS： The PD-1 level on CD8＋ T lymphocytes and the number of HBV specific CD8＋ T lymphocytes in patients and healthy controls （HCs） were analyzed by staining with pentameric peptide-human leukocyte antigen2 （HLA2） complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction （PCR） was used to measure the serum HBV- DNA levels. RESULTS： The level of PD-1 expression on total CD8＋ T cells in CHB patients （13.86% ± 3.38%） was significantly higher than that in AEHB patients （6.80%± 2.19%, P 〈 0.01） and healthy individuals （4.63% ± 1.23%, P 〈 0.01）. Compared to AEHB patients （0.81% ± 0.73%）, lower frequency of HBV-specific CD8＋ T cells was detected in chronic hepatitis B patients （0.37% ± 0.43%, P 〈 0.05）. There was an inverse correlation between the strength of HBV-specific CD8＋ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8＋ T cells in CriB and AEHB subjects （R = 0.541, P 〈 0.01）. However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase （ALT） levels （R = 0.066, P 〉 0.05）. CONCLUSION： Our results confirm previous reports that HBV specific CD8＋T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8＋ T cell response.

Pembrolizumab-emerging treatment of pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.

Significant benefits of pembrolizumab in treating refractory advanced pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Pulmonary sarcomatoid carcinoma(PSC),a rare subtype of non-small cell lung cancer(NSCLC),is poorly differentiated and highly aggressive.Treatment is limited,and the prognosis is poor.Pembrolizumab is an anti-programmed death(PD)-1 antibody with good efficacy in NSCLC.Recent studies have demonstrated that PD-ligand 1(PD-L1)overexpression is common in PSCs,which suggests that anti-PD-L1 treatment is an ideal option.However,the response to pembrolizumab in PSC has not been studied.CASE SUMMARY We present a PSC case with PD-L1 overexpression that significantly benefited from pembrolizumab.A 73-year-old Chinese male was detected with a right lung lesion.Pathological analysis of the right upper lobectomy confirmed PSC.The PDL1 test revealed overexpression(TPS:90%).Multiple metastases occurred 1 mo after surgery,representing stage IV PSC.Neither first-line chemotherapy nor second-line antiangiogenic agents showed any benefit.Radiotherapy(1200 cGy)was administered to relieve chest wall pain.The patient received the PD-1 inhibitor pembrolizumab(100 mg)as third-line therapy;however,because of fever and severe infection,he refused to receive immunotherapy any longer.Thus,only one dose of pembrolizumab was administered.Deep sustained remission of most of the metastases was achieved except for lesions in the right adrenal gland,which first shrank and then progressed.The patient died because of disease progression in the right adrenal gland.He achieved a progression-free survival time of 8 mo and an overall survival time of 9 mo with third-line pembrolizumab.CONCLUSION Our findings highlight and offer direct evidence of the efficacy of pembrolizumab in PD-L1-overexpressing PSCs.Combined radiotherapy and immunotherapy may enhance treatment efficacy.

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile,acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1(PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps,we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer withmitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-bdual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase(AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugatingmitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembledwith albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticleseffectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation ofPTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-b in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cellinfiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy toinhibit PTX@Alb-resistant tumors, further supporting its better clinical application。