***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 .  Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer .  Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Treating advanced or recurrent melanoma remains a challenge . Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 ( PD‐1 ) lig and s. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells , thus overcoming the immune resistance of cancer cells . Nivolumab has shown promising anticancer activity in various cancers . We carried out a single‐arm , open‐label , multicenter , phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma . Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v . nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity . The primary endpoint was overall response rate evaluated by an independent radiology review committee . The independent radiology review committee‐assessed overall response rate was 34.8 % ( 90 % confidence interval , 20.8–51.9 ) , and the overall survival rate at 18 months was 56.5 % ( 90 % confidence interval , 38.0–71.4 ) . Treatment‐related adverse events ( AEs ) of grade 3 or 4 only occurred in three patients ( 12.5 % ) . Two patients discontinued nivolumab because of AEs , but all AEs were considered manageable by early diagnosis and appropriate treatment . Subgroup analyses showed that nivolumab was clinical ly beneficial and tolerable regardless of BRAF genotype , and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival . In conclusion , nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma , with or without BRAF mutations . ( Trial registration no. JapicCTI‐142533 . Objectives To evaluate the prevalence and type of rheumatic immune-related adverse events ( irAEs ) in patients receiving immune checkpoint inhibitors ( ICIs )  , as well as the correlation with tumour response . Methods This was a single-centre prospect i ve observational study including all cancer patients receiving ICIs .  The occurrence of irAEs and tumour response was assessed on a regular basis . Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management . Results From September 2015 to May 2017 , 524 patients received ICIs and 35 were referred to the department of rheumatology ( 6.6 % ) . All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 lig and 1(PD-L1 ) antibodies , with a median exposure time of 70 days . There were two distinct clinical presentations : ( 1 ) inflammatory arthritis ( 3.8 % ) mimicking either rheumatoid arthritis ( n=7 ) , polymyalgia rheumatica ( n=11 ) or psoriatic arthritis ( n=2 ) and ( 2 ) non-inflammatory musculoskeletal conditions ( 2.8 % ; n=15 ) . One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide ( anti-CCP ) positive . Nineteen patients required glucocorticoids , and methotrexate was started in two patients . Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs , analgesics and /or physiotherapy . ICI treatment was pursued in all but one patient . Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs ( 85.7 % vs 35.3 % ; P<0.0001 ) . Conclusion Since ICIs are used with increasing frequency , knowledge of rheumatic irAEs and their management is of major interest . All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation . Furthermore , tumour response was significantly higher in patients who experienced rheumatic irAEs Background Programmed cell death protein-1 ( PD-1 ) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies . Treatment is generally well tolerated although immune-related adverse events ( irAEs ) can occur . Autoimmune thyroid dysfunction is among the most common irAE , but an assessment of the clinical , mechanistic , and immunologic features has not been previously described . Patient and methods Patients with advanced non-small-cell lung cancer ( NSCLC ) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center ( n = 51 ) as part of KEYNOTE-001 ( NCT01295827 ) were included . Thyroid function test and anti-thyroid antibodies were assessed prospect ively at each study visit , beginning before the first treatment . Frequency of development of thyroid dysfunction , association with anti-thyroid antibodies , clinical course , and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated . Results Of 51 patients treated , 3 were hypothyroid and 48 were not at baseline . Ten of 48 [ 21 % , 95 % confidence interval ( CI ) 10 % to 35 % ] patients developed thyroid dysfunction requiring thyroid replacement . Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction , compared with 3 of 38 who did not ( 80 % versus 8 % , P < 0.0001 ) . Thyroid dysfunction occurred early ( median , 42 days ) in the pembrolizumab course , and a majority ( 6 of 10 patients ) experienced brief , transient hyperthyroidism preceding the onset of hypothyroidism ; no persistent hyperthyroidism occurred . Both hyperthyroidism and hypothyroidism were largely asymptomatic . Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction ( hazard ratio , 0.29 ; 95 % CI 0.09 - 0.94 ; P = 0.04 ) . Conclusions Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset , frequently preceded by transient hyperthyroidism , closely associated with anti-thyroid antibodies , and may be associated with improved outcomes . The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to  receive  docetaxel  .  Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of  
    Output:
    
In patients treated with ICIs  , irAEs predict survival and response .
Although this correlation can not be fully explained , it may be related to the strongest T-cell activation