Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes.

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)-agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell-mediated immunotherapies.

CD8+ T-cell Immune Surveillance against a Tumor Antigen Encoded by the Oncogenic Long Noncoding RNA PVT1.

CD8+ T cells recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathologic conditions such as cancer. Advances in proteogenomic analysis of HLA ligandomes have demonstrated that cells present a subset of cryptic peptides derived from noncoding regions of the genome; however, the roles of cryptic HLA ligands in tumor immunity remain unknown. In the current study, we comprehensively and quantitatively investigated the HLA class I ligandome of a set of human colorectal cancer and matched normal tissues, showing that cryptic translation products accounted for approximately 5% of the HLA class I ligandome. We also found that a peptide encoded by the long noncoding RNA (lncRNA) PVT1 was predominantly enriched in multiple colorectal cancer tissues. The PVT1 gene is located downstream of the MYC gene in the genome and is aberrantly overexpressed across a variety of cancers, reflecting its oncogenic property. The PVT1 peptide was recognized by patient CD8+ tumor-infiltrating lymphocytes, as well as peripheral blood mononuclear cells, suggesting the presence of patient immune surveillance. Our findings show that peptides can be translated from lncRNAs and presented by HLA class I and that cancer patient T cells are capable of sensing aberrations in noncoding regions of the genome.

Proteogenomic identification of an immunogenic HLA class I neoantigen in mismatch repair-deficient colorectal cancer tissue.

Although CD8+ T cells recognize neoantigens that arise from somatic mutations in cancer, only a small fraction of nonsynonymous mutations give rise to clinically relevant neoantigens. In this study, HLA class I ligandomes of a panel of human colorectal cancer (CRC) and matched normal tissues were analyzed using mass spectrometry-based proteogenomic analysis. Neoantigen presentation was rare; however, the analysis detected a single neoantigen in a mismatch repair-deficient CRC (dMMR-CRC) tissue sample carrying 3967 nonsynonymous mutations, where abundant tumor-infiltrating lymphocytes (TILs) and inflamed gene expression status were observed in the tumor microenvironment (TME). Using the HLA class I ligandome data and gene expression profiles, a set of nonmutated tumor-associated antigen (TAA) candidates was concomitantly identified. Interestingly, CD8+ TILs predominantly recognized the detected neoantigen over the array of TAA candidates. Neoantigen-reactive CD8+ TILs showed PD-1 positivity and exhibited functional and specific responses. Moreover, T cell receptor (TCR) profiling identified the sequence of the neoantigen-reactive TCR clonotype and showed its expansion in the TME. Transduction of the sequenced TCR conferred neoantigen specificity and cytotoxicity to peripheral blood lymphocytes. The proteogenomic approach revealed the antigenic and reactive T cell landscape in dMMR-CRC, demonstrating the presence of an immunogenic neoantigen and its potential therapeutic applications.

[A Case in Which Multiple Post-Operatively Recurring Hepatocellular Carcinomas Showed a Positive Response to Sorafenib-Hepatic Arterial Infusion Chemotherapy (HAIC)Sequential Therapy].

A male patient in his 70s underwent a right lobectomy because of a hepatocellular carcinoma(HCC)located in the right lobe(S6)of his liver. Eleven months after surgery, contrast-enhanced CT showed multiple masses in the residual liver, which were diagnosed as HCC recurrence. He was then treated with hepatic arterial infusion chemotherapy(HAIC). Ten months after the recurrence, the liver tumors progressed. Therefore, treatment was switched to sorafenib(400 mg/day orally)and HAIC(low-dose FP: 5-FU 250 mg plus CDDP 5 mg 5 days/week 4 weeks)sequential therapy. The patient received 2 cycles of sorafenib-HAIC sequential therapy for 11 months, and his liver tumors shrunk considerably. Unfortunately, 24 months after the recurrence of HCC, he died of respiratory failure. The cause of his death was officially determined to be primary lung cancer. An autopsy revealed that most tissues were necrotic, and only a small number of viable tumor cells were present in the liver tumors. This suggests that sorafenib-HAIC sequential therapy was significantly effective in targeting the multiple HCCs in this case.

An incidental finding of low-grade appendiceal mucinous neoplasm during cesarean section: A case report.

Low-grade appendiceal mucinous neoplasms are rare and difficult to diagnose preoperatively because of a lack of characteristic symptoms. A 24-year-old female with no symptoms before pregnancy underwent an elective cesarean section at 38 weeks of gestation because of cephalo-pelvic disproportion. Although no abnormalities were detected in the newborn, uterus, or uterine adnexa, a sausage-like, swollen appendix was noted. The patient underwent appendectomy. Pathology showed the tumor was a low-grade appendiceal mucinous neoplasm.

The Antigen ASB4 on Cancer Stem Cells Serves as a Target for CTL Immunotherapy of Colorectal Cancer.

Colorectal cancer consists of a small number of cancer stem cells (CSC) and many non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because they survive conventional chemo- and radiotherapies and perpetuate tumor formation in vivo In this study, we conducted an HLA ligandome analysis to survey HLA-A24 peptides displayed by CSCs and non-CSCs of colorectal cancer. The analysis identified an antigen, ASB4, which was processed and presented by a CSC subset but not by non-CSCs. The ASB4 gene was expressed in CSCs of colorectal cancer, but not in cells that had differentiated into non-CSCs. Because ASB4 was not expressed by normal tissues, its peptide epitope elicited CD8+ cytotoxic T-cell (CTL) responses, which lysed CSCs of colorectal cancer and left non-CSCs intact. Therefore, ASB4 is a tumor-associated antigen that can elicit CTL responses specific to CSCs and can discriminate between two cellular subsets of colorectal cancer. Adoptively transferred CTLs specific for the CSC antigen ASB4 could infiltrate implanted colorectal cancer cell tumors and effectively prevented tumor growth in a mouse model. As the cancer cells implanted in these mice contained very few CSCs, the elimination of a CSC subset could be the condition necessary and sufficient to control tumor formation in vivo These results suggest that CTL-based immunotherapies against colorectal CSCs might be useful for preventing relapses. Cancer Immunol Res; 6(3); 358-69. ©2018 AACR.

Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model.

PURPOSE: Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of liver metastasis. This study evaluated the possibility that osteopontin (OPN) RNA interference (RNAi) and anti-OPN antibody (Ab) could have antimetastatic effects. METHODS: The differential gene expression was measured in a parental cell line, HPC-3, and an established highly liver metastatic cell line, HPC-3H4. This study investigated the effect of OPN RNAi and anti-OPN Ab on the metastatic ability of HPC-3H4 to the liver. An OPN RNAi-expressing vector was introduced into HPC-3H4 cells (HPC-3H4/miOPN), in which OPN production was reduced to the level of the parental HPC-3 cells. Finally, the ability of anti-OPN Ab to suppress liver metastasis was investigated. RESULTS: Osteopontin was upregulated 11.1-fold in HPC-3H4 in comparison to HPC-3. The metastatic rate of HPC-3H4/miOPN was significantly reduced to 25% in comparison to the 100% metastatic rate of HPC-3H4 and control HPC-3H4/miNeg cells (P < 0.01). The metastatic rate of the group given anti-OPN Ab was 50%. CONCLUSION: OPN RNAi and anti-OPN Ab had remarkable inhibitory effects against liver metastasis by the pancreatic cancer cell line.

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: a prospective randomized trial.

PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.

Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer.

BACKGROUND: We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. METHODS: We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1-1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. RESULTS: In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-gamma responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. CONCLUSION: This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.

Inhibitory effect of endothelin A receptor blockade on tumor growth and liver metastasis of a human gastric cancer cell line.

BACKGROUND: With metastatic progression, gastric cancer is incurable. Using a DNA microarray, we performed differential gene expression analysis of established highly metastatic gastric cancer cell lines and compared the findings with those from a low-metastatic parental cell line. The results demonstrated that the endothelin A receptor (ET-A) gene was the only one from the highly metastatic cell lines that was generally up-regulated. METHODS: To investigate the role that ET-A plays in gastric cancer metastasis, we studied the effect of an ET-A-selective antagonist, YM598, on cell proliferation, tumor growth, and liver metastasis of the highly liver metastatic cell line AZ-H5c, established from the low metastatic human gastric cancer cell line AZ-521. RESULTS: An in vivo study using nude mice demonstrated that YM598 had a significant growth inhibition effect on AZ-H5c at doses of 0.5-10.0 mg/kg. The liver metastatic rate was also significantly reduced by YM598: control, 83.3%; 1 mg/kg dosage, 16.7%; 10 mg/kg, 20%; and pretreatment at 1 mg/kg, 16.7%. There was no evidence of gross toxicity resulting from the YM598 treatment. CONCLUSION: The ET-A blockade by YM598 had a strong inhibitory effect against tumor growth and liver metastasis of the gastric cancer cell lines. These data suggest that YM598 has potential as a novel therapeutic agent for inhibiting liver metastasis of gastric cancer.

Anastomotic suture line recurrence of early rectal carcinomas that had been resected by laparoscopic surgery.

We report herein a case of a 64-year-old woman found to have anastomotic suture line recurrence of an early rectal carcinoma. The patient had undergone laparoscopy-assisted low anterior rectal resection for an early rectal carcinoma 2 years before the anastomotic site recurrence. A follow-up colonoscopy revealed an elevated lesion on the anastomotic suture line. The diagnosis of adenocarcinoma was confirmed by biopsy. The patient underwent a resection of the remnant rectum. Histological examination of the resected specimen showed that the anastomotic site recurrence might have been caused by intraluminal implantation from the primary rectal cancer. We speculate that intraluminal implantation might be caused by insufficient intraoperative rectal irrigation because of limited access often encountered in laparoscopic surgery. We propose that it is necessary to devise a method with which to perform sufficient intraoperative rectal irrigation in laparoscopic surgery for rectal carcinoma.

A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis.

Caspase-associated recruitment domains (CARD) are protein-protein interaction modules found extensively in proteins that play important roles in apoptosis. One of the CARD-containing proteins, TUCAN (CARD8), was reported previously as an antiapoptotic protein with a molecular weight of 48 kDa, which was up-regulated in colon cancer cells. We identified a novel isoform of TUCAN with a molecular weight of 54 kDa. The new variant of TUCAN, termed TUCAN-54, was expressed in gastric, colon, and breast cancer tissues but was barely detected in normal noncancerous tissues, whereas 48-kDa TUCAN was detected in tumor tissues and noncancerous tissues. To know the function of TUCAN-54 in the apoptosis of cancer cells, TUCAN-54 was overexpressed in tumor cells by gene transfection. Its overexpression inhibited pro-caspase-9 activation, leading to the suppression of the cell death induced by a protein kinase inhibitor, staurosporine, or a chemotherapeutic reagent, etoposide (VP-16). In contrast, specific small interfering RNA-mediated suppression of TUCAN-54 expression in tumor cells increased the VP-16-induced cell death rate, indicating that expression of TUCAN-54 might be associated with chemoresistance of tumor cells. In addition, it inhibited caspase-8 activation as well, thereby suppressing Fas-induced cell death. It was revealed that Fas-associated death domain was physically associated with TUCAN-54 but not with 48-kDa TUCAN. Thus, TUCAN-54 might be a novel tumor-specific antiapoptotic molecule expressed in a variety of human cancer tissues, which might aggravate malignant potential of cancer cells, such as chemoresistance and immunoresistance.

A novel, easy, and safe technique to repair a stoma prolapse using a surgical stapling device.

A stoma prolapse is one of the late complications and often occurs when the stoma is made in an emergency situation. This complication is not lethal, but causes irritable stoma, skin trouble, and difficulty in stoma care. We herein report the case of a 48-year-old female with an end colostomy that was created as an emergency operation 4 months before. On admission, her colostomy protruded approximately 20 cm from the skin with marked redness, swelling, and erosion; it was impossible to treat manually. We repaired the prolapse successfully in a simple procedure with a Proximate Linear Cutter 100. Briefly, under mild sedation, the instrument was diagonally inserted into the prolapsed stoma and applied twice on both sides. Then, the base of each divided tissue was stapled and cut with the same device. Finally, the prolapse was completely repaired without major bleeding and severe pain. We have applied this novel technique successfully in 5 further cases, and there have been no complications or recurrences. This technique can be performed without spinal or general anesthesia and seems to be a very useful procedure for patients with prolapse of a stoma.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2003 and March 2004].

Tendency of isolated bacteria from infections in general surgery during the period from April 2003 to March 2004 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 455 strains including 14 strains of Candida spp. were isolated from 191(75.2%) of 254 patients with surgical infections. Two hundred and thirty-nine strains were isolated from primary infections, and 216 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria and aerobic Gram-negative bacteria were predominant, while aerobic Gram-positive bacteria were predominant from postoperative infections. The isolation rate of aerobic Gram-positive bacteria, such as Enterococcus spp. and Staphylococcus aureus were higher from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa in this order, and from postoperative infections, E. coli was the most predominantly isolated, followed by P. aeruginosa, E. cloacae, and K. pneumoniae. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. The isolation rate of anaerobic Gram-positive bacteria from primary infections and that of aerobic Gram-positive bacteria from postoperative infections were high in the last several years. In this series, we noticed no vancomycin-resistant Gram-positive cocci, but a few strains of moderately arbekacin-resistant MRSA. Carbapenm-resistant P. aeruginosa was seen in less than 10 per cents. Last year we noticed that there were cefazolin-resistant E. coli producing extended spectrum beta-lactamase, but there was no highly cefazolin-resistant E. coli in this year. In the next series, increase of both anaerobic bacteria and Enterococcus spp. should be carefully followed up.

Peptide-based vaccination for colorectal cancer.

Recently, the number of patients with colorectal cancer has been increasing. Although most patients with early colorectal cancer have a good prognosis, in the case of recurrent or metastatic disease, the prognosis is poor and most patients will ultimately die of cancer. Furthermore, the conventional treatment, such as chemotherapy or radiation therapy, occasionally can not be continued due to reasons of toxicity and/or poor response. Therefore, novel therapeutic optional approaches based on immunotherapy are being explored at present. This review describes and sums up the principles and the longstanding problems of peptide vaccine therapy, and demonstrates the results of clinical trials with colorectal cancer peptide vaccine therapy, including the authors' personal appraisal. In conclusion, the future prospects of peptide vaccine therapy are described.

A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins.

We reported previously a HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) CTL. This peptide was derived from survivin protein, an inhibitor of apoptosis proteins, expressed in a variety of tumors, such as adenocarcinoma, squamous cell carcinoma, and malignant melanoma. In this report, we provide further evidence that survivin-2B80-88 peptide might serve as a potent immunogenic cancer vaccine for various cancer patients. Overexpression of survivin was detected in surgically resected primary tumor specimens of most breast and colorectal cancers and some gastric cancers as assessed by immunohistochemical study. HLA-A24/survivin-2B80-88 tetramer analysis revealed that there existed an increased number of CTL precursors in peripheral blood mononuclear cells (PBMC) of HLA-A24(+) cancer patients, and in vitro stimulation of PBMCs from six breast cancer patients with survivin-2B80-88 peptide could lead to increases of the CTL precursor frequency. Furthermore, CTLs specific for this peptide were successfully induced from PBMCs in all 7 (100%) patients with breast cancers, 6 of 7 (83%) patients with colorectal cancers, and 4 of 7 (57%) patients with gastric cancers. These data indicate that survivin expressed in tumor tissues is antigenic in cancer patients, and survivin-2B80-88-specific CTLs are present in PBMCs of various cancer patients. Our study raises the possibility that this peptide may be applicable as a general cancer vaccine to a large proportion of HLA-A24(+) cancer patients.

Vascular endothelial growth factor C promotes lymph node metastasis in a rectal cancer orthotopic model.

PURPOSE: Vascular endothelial growth factor C (VEGF-C), a novel member of the vascular endothelial growth factor family, is a relatively specific lymphangiogenic growth factor. It has been suggested that increased expression of VEGF-C in primary tumors is correlated with lymph node metastasis. We conducted this study to determine whether VEGF-C directly affects lymphangiogenesis and lymph node metastasis in colorectal cancer. METHODS: For an accurate analysis and clear visualization of metastases, the rectal cancer cell line, DLD1, was engineered to stably express green fluorescent protein (GFP) (DLD1/GFP). We implanted DLD1/GFP cells overexpressing VEGF-C orthotopically into the rectal walls of nude mice. RESULTS: Lymph node metastasis was confirmed in all (100%) of the mice bearing DLD1/GFP-VEGF-C tumors, but in only 25% of the mice bearing control tumors. There were more lymph node metastases per mouse in the mice bearing DLD1/GFP-VEGF-C tumors than in the mice bearing control tumors. There were no differences in cell growth and motility in vitro or in the resulting tumor volume from the implanted cells between the two groups. Immunohistochemical staining revealed that VEGF-C induced the growth of lymphatic vessels, which were enlarged in the tumor periphery and contained tumor cell emboli. CONCLUSION: These results suggest that VEGF-C-induced lymphangiogenesis mediates tumor spread and the formation of lymph node metastasis.

Pancreas-sparing duodenectomy for a recurrent retroperitoneal liposarcoma: report of a case.

Pancreas-sparing duodenectomy (PSD), which allows preservation of the pancreas in its entirety, is a promising procedure for low-grade malignancies of the duodenum, the periampullary region, and the neighboring retroperitoneum. We report a case of recurrent retroperitoneal liposarcoma involving the second and third parts of the duodenum, which was extirpated using PSD, after a right hemicolectomy for tumor invasion of part of the colonic hepatic flexura. The Roux-en-Y jejunal limb was sutured to the duodenal bulb in an end-to-end fashion, and the biliary and pancreatic duct systems were reconstructed with end-to-side anastomoses, placing the jejunal limb distal to the bulbo-jejunostomy after a septoplasty to repair the adjacent pancreatic and biliary ducts. Because retroperitoneal liposarcoma has a low incidence of lymph node metastasis, pancreaticoduodenectomy may be inappropriate, especially if minimally extensive surgery can ensure organ preservation. Pancreas-sparing duodenectomy could be the most appropriate procedure for nonepithelial malignant tumors located around the duodenum distal to the pylorus, which have no involvement with the pancreatic parenchyma or periduodenal lymph nodes.

[Anti-apoptosis protein, survivin-2B-derived peptide vaccine therapy].

As advances in new therapeutic modalities are urgently needed, one of which is tumor-specific immunotherapy. We identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88, and started a phase I clinical study of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities. In 6 patients, tumor marker levels decreased transiently during the period of vaccination. Slight reduction in tumor volume was observed in one patient, which was considered a minor responder. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL after vaccination. This phase I clinical study revealed that administration of the survivin-2B peptide is safe. The vaccination with survivin-2B peptide alone was not enough to elicit clinical responses. Consequently, we have recently started the second clinical study of survivin-2B peptide vaccine in combination with various adjuvants.

Gastric T-cell lymphoma associated with hemophagocytic syndrome.

BACKGROUND: Lymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma has never been reported. Here we report a case of gastric T-cell lymphoma-associated hemophagocytic syndrome. CASE PRESENTATION: A 51-year-old woman presented with pain, redness of breasts, fever and hematemesis. Hematological examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the stomach and the computed tomography scan showed liver tumor. She underwent total gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th postoperative day. Autopsy revealed it to be a LAHS. CONCLUSIONS: If Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract, bleeding from the primary lesion might be uncontrollable. Early diagnosis and appropriate treatment are needed for long-term survival.