Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Monitored anesthesia care and asleep-awake-asleep techniques combined with multiple monitoring for resection of gliomas in eloquent brain areas:a retrospective analysis of 225 patients

Background:Awake craniotomy(AC)has become gold standard in surgical resection of gliomas located in eloquent areas.The conscious sedation techniques in AC include both monitored anesthesia care(MAC)and asleep-awake-asleep(AAA).The choice of optimal anesthetic method depends on the preferences of the surgical team(mainly anesthesiologist and neurosurgeon).The aim of this study was to compare the difference in physiological and blood gas data,dosage of different drugs,the probability of switching to endotracheal intubation,and extent of tumor resection and dysfunction after operation between AAA and MAC anesthetic management for resection of gliomas in eloquent brain areas.Methods:Two-hundred and twenty-five patients with super-tentorial tumor located in eloquent areas underwent AC from 2009 to 2021 in Xijing Hospital.Forty-one patients underwent AAA technique,and the rest one-hundred eighty-four patients underwent MAC technique.Anesthetic management,dosage of different drugs,intraoperative complications,postoperative outcomes,adverse events,extent of resection and motor,and sensory and language dysfunction after operation were compared between MAC and AAA.Result:There was no significant difference in gender,KPS score,MMSE score,glioma grade,type,and growth site between the patients in the two groups,except the older age of patients in MAC group than that in AAA group.During the whole process of operation,there were greater pulse pressure difference(P=0.046),shorter operation time(P=0.039),less dosage of remifentanil(P=0.000),more dosage of dexmedetomidine(P=0.013),more use of antiemetics(81%,P=0.0067),lower use of vasoactive agent(45.1%,P=0.010),and lower probability of conversion to general anesthesia(GA,P=0.027)in MAC group than that in AAA group.Blood gas analysis showed that PetCO2(P=0.000),Glu concentration(P=0.000),and PaCO2(P=0.000)were higher,but SPO2(P=0.002)and PaO2(P=0.000)were lower in MAC group than that in AAA group.In the postoperative recovery stage,compared with that of AAA group,the probability of dysfunction in MAC group at 1,3,5,and 7 days after operation was lower,which were 27.8%vs 53.6%(P=0.003),31%vs 68.3%(P=0.000),28.8%vs 63.4%(P=0.000),and 25.6%vs 58.5%(P=0.000),respectively.Conclusion:Compared with AAA,it seems that MAC has more advantages in the management for resection of gliomas in eloquent brain areas,and MAC combined with multiple monitoring such as cerebral cortical mapping,neuronavigation,and ultrasonic detection is worthy of popularization for the resection of gliomas in eloquent brain areas.