radiotherapy is one of the treatments used for most types of cancer , regardless of the clinical stage . it is generally accepted that radiotherapy induces cancer cell death via apoptosis and/or necrosis by damaging ( either directly or indirectly ) the dna . if irradiation could induce cell death just by damaging the dna , the effect would be seen only within the irradiated field . however , the cytoreductive effects on the distant metastatic lesions outside the irradiated field , known as  abscopal effect  , have been observed in patients with melanoma , lung cancer , and renal cancer , among others 1 . the emerging evidence suggests that the immunogenic cell death caused by irradiation might be another important effect of radiotherapy , in addition to the dna damage 3 . radiationinduced cell death elicits the damage signals , such as highmobility group box 1 ( hmgb1 ) , which trigger the activation of antigen presentation cells ( apcs ) . subsequently , apcs present the tumorderived antigens to cytotoxic t lymphocytes ( ctls ) , which then kill the target cells . radiotherapy also increases the expression of hla class i molecules , which also can activate ctls by presenting tumorderived antigen , on the surface of tumor cells 4 . the abscopal effect has been reported several times over the years , reviving the interest in the progress of cancer immunology 5 . accumulating evidence shows that the combination of radio and immunotherapy ( e.g. , using immune checkpoint inhibitors ) induces the abscopal effect in several types of cancers 2 , 6 , 7 , 8 . these reports suggest that the combined radio and immunotherapy can be an effective strategy for advanced or recurrent cancers . here , we report a case of postoperative , locally and peritoneally disseminated , recurrent gastric cancer treated using a concomitant radiotherapy and adoptive tcell immunotherapy . the treatment had an abscopal effect and achieved a complete remission of the irradiated tumor . a 54yearold japanese male was diagnosed with gastric cancer and underwent distal gastrectomy with billrothi . the histology and pathological stage of the tumor were poorly differentiated adenocarcinoma and pt4an3am0 ( stage iiic ) with no residual tumor , respectively . however , 10 months after the surgery , a local recurrence ( invasion of the pancreas and the left kidney ) and peritoneal dissemination with cancerous peritonitis were diagnosed using computed tomography ( ct ) and endoscopic biopsy . then , another chemotherapy treatment ( paclitaxel ) was prescribed . the chemotherapy had to be stopped after two courses because of a hematological adverse effect ( neutrophil count decreased to < 1000/mm ) . the patient was referred to the outpatient clinic to undergo the adoptive tcell immunotherapy and dendritic cell ( dc ) therapy ; details of the therapies are described elsewhere 9 . briefly , 310  10 adoptive t cells and 110  10 dcs were infused intravenously and intratumorally , respectively , at intervals of approximately 2 weeks . however , after four courses of the therapies , a progression of local recurrence and peritoneal dissemination was observed . subsequently , the patient received 48 gy in 24 fractions of radiotherapy using the intensitymodulated radiotherapy ( imrt ) method ( fig . figure 2 shows changes in local recurrence and peritoneal dissemination before , during , and after immunoradiotherapy . during immunoradiotherapy , shrinkage of the locally reoccurred tumor two months after the initiation of radiotherapy , the performance status was improved from 4 to 2 , and ct images showed a complete remission of the locally recurrent tumor . furthermore , the shrinkage of metastatic peritoneal tumor ( i.e. , the abscopal effect ) was observed ( fig . however , the abscopal effect lesions could not be measured because they consisted of small ( < 5 mm ) multiple nodular peritoneal dissemination : lesions < 10 mm are categorized into after completion of the immunoradiotherapy , the adoptive tcell immunotherapy was continued ( 11 courses ) . however , 5 months after the immunoradiotherapy , the patient died because of new multiple distant metastases in the peritoneum . figure 3 shows the clinical time course and the corresponding changes in the serum tumor marker ( cea , ca199 ) after postoperative recurrence . ( a ) radiotherapy ( 48 gy in 24 fractions ) using the imrt method was prescribed for local recurrent tumor , which includes the pancreas and the left kidney . ( b ) the metastatic peritoneal tumor in which the abscopal effect was observed was not included in the irradiated field . ct images of local recurrence and peritoneal dissemination before , during , and after immunoradiotherapy . ( a ) ct images before immunoradiotherapy : 2 months after the first paclitaxel treatment followed by immunotherapy . progression of the local recurrence lesion and peritoneal dissemination was confirmed . ( b ) ct image was acquired during immunoradiotherapy at 44 gy in 22 fractions point . shrinkage of the locally reoccurred tumor ( red arrow ) and progression in peritoneal dissemination ( red circle ) were observed . ( c ) ct image was taken 2 months after the start of the therapy . irt , immunoradiotherapy . the clinical time course and corresponding changes in the serum tumor marker after postoperative recurrence . ca199 temporally decreased in response to complete remission of the locally recurrent tumor and abscopal effect after immunoradiotherapy , whereas cea steadily increased . ptx , paclitaxel ; dc , dendritic cell ; rt , radiotherapy ; irt , immunoradiotherapy . in this case , we observed an abscopal effect and a complete local response of the recurrent gastric cancer to a multimodal therapy . the treatment consisted of 48 gy in 24 fractions of radiotherapy and concurrent tcell immunotherapy . to date , the optimal irradiation dose for recurrent gastric cancer is unknown . previous studies have demonstrated that neoadjuvant chemoradiotherapy ( using 45 gy in 25 fractions ) showed a pathological complete response rate of 1630% 10 . from these data , 48 gy in 24 fractions seemed to be an insufficient dose to achieve a complete response on its own . it suggested that the combination therapy not only caused the abscopal effect but also affected the locally irradiated tumor . to confirm the mechanism and obtain a detailed validation of the immune response , the immune status and tumor environment should be examined by analyzing the tumorinfiltrating t lymphocytes and the expression of hla class i molecules . however , this was ethically unfeasible because of the worsening general health of the patient . reynders et al . have reviewed five recent clinical case reports showing an abscopal effect after radiotherapy combined with immunotherapy 11 . the studies have used various radiation doses ( 24 gy in 3 fractions , 28.5 gy in 3 fractions , 30 gy in 5 fractions , 54 gy in 3 fractions , and 58 gy in 29 fractions ) , examined varied histology ( melanoma and lung adenocarcinoma ) , and employed different types of immunotherapy ( ipilimumab and bcg vaccine ) . hence , the optimal dose and number of fractions to achieve the abscopal effect has remained unclear . interestingly , the abscopal effect was observed after the shrinkage of the locally reoccurred tumor suggesting that the activation of systemic immunestimulation through elicited damage signals followed by radiationinduced cell death plays a critical role in the abscopal effect . accumulating evidence suggests that a dysfunction in the host systemic immunity and/or low immunogenic characteristics of the tumor may favor the progression of cancer 12 . therefore , the therapies restoring or strengthening the immune functions might constitute an effective treatment . kim et al . have reported that tcellbased immunotherapy destroys the human gastric cancer cells ( mkn74 ) in vitro and inhibits the growth of these cells in the nude mouse 13 . recent studies have shown that radiotherapy can act as an immunostimulant , causing the immunogenic cell death and releasing the danger signals such as hmgb1 14 , 15 . we have also shown that chemoradiotherapy releases hmgb1 and induces tumor antigenspecific tcell response in esophageal cancer patients 16 , and that hyperthermochemoradiotherapy enhances the hla class i expression in rectal cancer patients 16 , 17 . these results suggest that radiotherapy could be profitably combined with immunotherapy . with the recent advances in diagnostic and treatment modalities , the prognosis of gastric cancer has become more favorable , particularly in the early stages . however , the postoperative recurrence is one of the most crucial factors associated with the cancerrelated deaths of gastric cancer patients 18 . have reported such recurrence ( local , peritoneal , and hematogenous ) in 29.9% of patients , including those who had undergone radiotherapy and/or chemotherapy as adjuvant treatment 19 . they observed a rate of 24.2% and 19.3% for local and peritoneal recurrence , respectively , with the median survival period of only 9.1 and 2.7 months after local and peritoneal recurrence , respectively . recently , yang et al . have reported that the combined intravenous and intraperitoneal chemotherapy effectively prevents peritoneal recurrence . a metaanalysis has shown that this therapy prolongs the survival period in comparison with intravenous chemotherapy alone 20 . nivolumab , a pd1 immune checkpoint inhibitor antibody , has shown a significant superiority over chemotherapy in phase iii trials for melanoma and squamous cell carcinoma of the lung 21 , 22 . however , despite prolonged survival , the disease progression rate has remained around 30% . these results suggest that immunotherapy should be combined with an effective local treatment , such as radiotherapy . hence , immunoradiotherapy is a promising treatment for postoperative recurrent gastric cancer , although further investigation is warranted . written informed consent was obtained from the patient , agreeing to the publication of this case report and any accompanying images . ys , yy , sn , ts , and tn : coordinated the clinics , prescribed and carried out the immunotherapy , and participated in the followup of the patient .
key clinical messagethe mechanism of abscopal effect is becoming clear by the progress of cancer immunology . 
 a 54yearold male with recurrent gastric cancer presented an abscopal effect after radiotherapy with concurrent adoptive tcell immunotherapy ( immunoradiotherapy ) . 
 immunoradiotherapy has potential to induce abscopal effect by strengthening systemic antitumor immunity even in recurrent cancer .