Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed ...Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.展开更多
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-...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.展开更多
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 ant...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.展开更多
AIM: To define the potential role of programmed death-1/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...AIM: To define the potential role of programmed death-1/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 (CHB) and acute exacerbation of hepatitis B (AEHB) infection. METHODS: The PD-1 level on CD8+ T lymphocytes and the number of HBV specifi c 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 CHB 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 with 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.展开更多
文摘Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.
文摘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.
文摘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.
文摘AIM: To define the potential role of programmed death-1/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 (CHB) and acute exacerbation of hepatitis B (AEHB) infection. METHODS: The PD-1 level on CD8+ T lymphocytes and the number of HBV specifi c 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 CHB 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 with 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.
