Strategies in comprehensive therapy for gastrointestinal (GI) cancer have been optimized in the last decades to improve patients' outcomes. However, treatment options remain limited for late-stage or refractory diseases. The efficacy of immune checkpoint inhibitors (ICIs) for treatment of refractory GI cancer has been confirmed by randomized clinical trials. In 2017, pembrolizumab was approved by the US Food and Drug Administration as the first agent for treatment of metastatic solid tumors with mismatch repair deficiency, especially for colorectal cancer. Given the different mechanisms, oncologists have focused on determining whether ICIs-based combination strategies could achieve higher efficacy than conventional therapy alone in late-stage or even front-line treatment of GI cancer. This review discusses the current status of combining immune checkpoint inhibitors with molecular targeted therapy, chemotherapy, or radiotherapy in GI cancer in terms of mechanisms, safety, and efficacy to provide basis for future research.
Combined Modality Therapy ; methods ; Gastrointestinal Neoplasms ; immunology ; therapy ; Humans ; Immunotherapy ; methods ; trends ; Randomized Controlled Trials as Topic

No abstract available.
Aged ; Antigens, CD38/analysis ; Biomarkers, Tumor/analysis ; Biopsy ; Gastrointestinal Hemorrhage/diagnosis/*etiology/therapy ; Gastroscopy ; Hematemesis/etiology ; Humans ; Immunohistochemistry ; Male ; Melena/etiology ; Membrane Glycoproteins/analysis ; Multiple Myeloma/*complications/immunology/pathology/therapy ; Recurrence ; Stomach Neoplasms/*complications/immunology/pathology/therapy

OBJECTIVETo study the clinicopathologic features, immunophenotype, histological diagnosis and prognosis of hepatic epithelioid angiomyolipoma.

METHODSClinical data of 25 cases of hepatic epithelioid angiomyolipoma were collected along with follow-up study of the patients. The pathological features were documented and immunohistochemical study of various markers was performed with an emphasis on diagnosis and differential diagnosis.

RESULTSHepatic epithelioid angiomyolipoma was more commonly found in young women without characteristic clinical symptoms. Its morphological features were characterized by marked cytological atypia, relatively rare mitotic figures; radial distribution of tumor cells around the thin-walled blood vessels or muscular vessels; and the presence of common multinucleated giant cells and large ganglion-like tumor cells. The tumor cells expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers (SMA). Tumor cells expressed various other markers including ER 16% (4/25), PR 32% (8/25), TFE3 24% (6/25) and p53 60% (15/25).

CONCLUSIONSHepatic epithelioid angiomyolipoma has variable morphological features and characteristic immunohistochemical phenotype. The differential diagnoses include a variety of tumors. The biological behavior of the tumor tends to be benign.

Age Factors ; Angiomyolipoma ; genetics ; immunology ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; Giant Cells ; pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; Liver Neoplasms ; genetics ; immunology ; metabolism ; pathology ; MART-1 Antigen ; metabolism ; Melanoma-Specific Antigens ; metabolism ; Muscle, Smooth ; metabolism ; Prognosis

Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific context. Here we summarize the role of different inflammasome complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro-inflammatory cytokines play in immunity.
Animals ; Carcinoma ; immunology ; pathology ; therapy ; Gastrointestinal Neoplasms ; immunology ; pathology ; therapy ; Humans ; Inflammasomes ; metabolism ; Melanoma ; immunology ; pathology ; therapy ; Neoplasms ; immunology ; pathology ; therapy ; Skin Neoplasms ; immunology ; pathology ; therapy

Classification ; methods ; Dermatofibrosarcoma ; classification ; pathology ; Gastrointestinal Stromal Tumors ; immunology ; pathology ; Hemangioendothelioma ; classification ; metabolism ; pathology ; Humans ; Neoplasms, Connective and Soft Tissue ; classification ; metabolism ; pathology ; Neurilemmoma ; pathology ; Rhabdomyosarcoma ; metabolism ; pathology ; Sclerosis ; World Health Organization

Actins ; immunology ; metabolism ; Antibodies, Monoclonal ; metabolism ; Child ; Diagnosis, Differential ; Fibroma ; metabolism ; pathology ; surgery ; Follow-Up Studies ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Gastrointestinal Stromal Tumors ; metabolism ; pathology ; Humans ; Leiomyoma ; metabolism ; pathology ; Male ; Pyloric Antrum ; pathology ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Despite a higher incidence and less favorable outcome of malignant tumors in obese patients, much less recognized is the link between obesity and cancer. The mechanism of the association of obesity with carcinogenesis remains incompletely understood. Postulated mechanisms include insulin resistance, insulin-like growth factor signaling, chronic inflammation, immunomodulation, hyperglycemia-induced oxidative stress, and changes of intestinal microbiome. Insulin resistance leads to direct mitogenic and antiapoptotic signaling by insulin and the insulin-like growth factor axis. Obesity can be considered to be a state of chronic low-grade inflammation. In obesity, numerous proinflammatory cytokines are released from adipose tissue which may involve in carcinogenesis. Hyperglycemia in susceptible cells results in the overproduction of superoxide and this process is the key to initiating all damaging pathways related to diabetes. This hyperglycemia-induced oxidative stress could be one possible link among obesity, diabetes, and cancer development. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention.
Adipokines/metabolism/physiology ; Gastrointestinal Neoplasms/*etiology/microbiology ; Humans ; Inflammation/etiology ; Insulin/metabolism/physiology ; Leptin/metabolism/physiology ; Obesity/*complications/immunology/metabolism ; Oxidative Stress ; Somatomedins/metabolism/physiology

OBJECTIVETo verify the clinical therapeutic effect of warming needle moxibustion on improvement of the gastrointestinal and immune function in patients with postoperation of colorectal cancer.

METHODSOne hundred and five patients with postoperation of colorectal cancer were randomly divided into an acupuncture and moxibustion group, a Chinese medicine group and a routine treatment group, 35 cases in each group. They were all treated with gastrointestinal decompression and fluid replacement after operation. The acupuncture and moxibustion group was also treated with warming needle moxibustion on the 1st day after operation, and Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) etc. were selected, once a day for 10 days, and the Chinese medicine group with Simo Decoction oral solution, three times daily for 10 days. The gastrointestinal function, peripheral blood components and changes of T lymphocyte and NK cells in postoperative patients were observed.

RESULTSThe time of the first bowel sound, exhaust and defecation in the acupuncture and moxibustion group were all shorter than those in the Chinese medicine group and the routine treatment group (P<0.05, P<0.01). On the 10th day after operation, the percentages distribution of lymphocyte and neutrophil in the acupuncture and moxibustion group were better than those in the Chinese medicine group and the routine treatment group (all P<0.05). The acupuncture and moxibustion group was also superior to the Chinese medicine group and the routine treatment group in improving the subgroup of T lymphocyte, NK cells and the digestive system symptoms (all P<0.05).

CONCLUSIONWarming needle moxibustion has a good therapeutic effect on gastrointestinal function and can regulate bidirectionally peripheral blood lymphocyte and neutrophile granulocyte and improve the T lymphocyte subgroup and NK cells so as to promote the recovery of immune function in patients with colorectal cancer after operation.

Acupuncture Therapy ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; immunology ; physiopathology ; surgery ; therapy ; Female ; Gastrointestinal Tract ; immunology ; physiopathology ; Humans ; Immune System ; immunology ; Male ; Middle Aged ; Moxibustion ; Postoperative Period ; Young Adult

OBJECTIVETo explore the effects of postoperative enteral immunonutrition on inflammatory response and immunologic function in patients with gastrointestinal tumor.

METHODSClinical data of 106 gastrointestinal malignant tumor patients with malnutrition who were treated in the Department of General Surgery, the People's Hospital of Cangzhou in Hebei province from January 2008 to June 2010 were prospectively collected. Patients were randomized into two groups, including enteral immunonutrition group(n=53) and common enteral nutrition group(n=53). Related immunological indices and C-reaction protein were measured on preoperative day 5 and postoperative day 1 and 9.

RESULTSThe general information and preoperative immunological indices were comparable between the two groups(P>0.05). On postoperative day 9, levels of CD4, CD4/CD8, IgG, lymphocyte, NK cells, and complement C3, C4, and CH50 in the enteral immunonutrition group were higher than those in common enteral nutrition group. Serum C-reaction protein level was lower than that in control group, and the difference was statistically significant (P<0.05). Postoperative infection rate was 3.8%(2/53) in enteral immunonutrition group, significantly lower than that in control group with an infection rate of 15.1%(8/53)(P<0.05). The mean postoperative hospital stay of the two groups were (8.1±1.1) d and (9.2±2.1) d, respectively, and the difference was statistically significant(P<0.05).

CONCLUSIONFor gastrointestinal malignant tumor patients with malnutrition, the use of enteral immunonutrition can alleviate the postoperative trauma and inflammatory response, improve the immune function, thus can reduce the occurrence of postoperative infection, and accelerate patient recovery.

Adolescent ; Adult ; Aged ; C-Reactive Protein ; analysis ; CD4-CD8 Ratio ; Complement System Proteins ; immunology ; Enteral Nutrition ; Female ; Gastrointestinal Neoplasms ; complications ; immunology ; therapy ; Humans ; Inflammation ; immunology ; Killer Cells, Natural ; immunology ; Male ; Malnutrition ; complications ; therapy ; Middle Aged ; Postoperative Period ; Prospective Studies ; Treatment Outcome ; Young Adult

BACKGROUNDMany types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor.

METHODSA total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups: high-risk group (tumor markers positive group) and low-risk group (tumor markers negative group). The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry.

RESULTSPercentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers (P < 0.05), especially on the surface of NK cells (P < 0.01). Compared with the low-risk group, there was a significant reduction of HLA class I on peripheral T lymphocytes (P < 0.05) and NK cells (P < 0.05) in the high-risk group.

CONCLUSIONSHLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

Adult ; Aged ; Biomarkers, Tumor ; analysis ; Down-Regulation ; Female ; Gastrointestinal Neoplasms ; immunology ; Histocompatibility Antigens Class I ; analysis ; Humans ; Killer Cells, Natural ; immunology ; Male ; Middle Aged ; T-Lymphocytes ; immunology