Cancer immunoediting consists of three sequential phases: elimination, equilibrium, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibrium phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi (Spleen)-deficiency. Classic quotations, immune evidence and clinical observations suggest that Spleen (but not other organs) deficiency is the key pathogenesis of colorectal cancer (CRC) microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-derived immunosuppressive factors and surrendered immune cells-regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages (TAMs) constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting.
Colorectal Neoplasms ; immunology ; Humans ; Immune Evasion ; Immunosuppression ; Spleen ; immunology ; Syndrome ; Tumor Microenvironment ; immunology

With the development of tumor immunology research, it has been recognized that the anti-tumor immune system function is better to predict the prognosis. Relationship between the tumor-infiltrating lymphocytes (TIL) and colorectal cancer has become one of the hot topics in research. Here we summarize the latest studies about the relationship between the TIL and clinicopathological factors, prognosis and microsatellite instability (MSI).
Colorectal Neoplasms ; genetics ; immunology ; pathology ; Humans ; Lymphocytes, Tumor-Infiltrating ; immunology ; Microsatellite Instability ; Prognosis

Antigens, Neoplasm ; metabolism ; Antigens, Surface ; metabolism ; Colorectal Neoplasms ; immunology ; pathology ; Humans ; Prognosis ; Trophoblasts ; immunology

Ulcerative colitis is a non-specific colorectal inflammation of unknown causes. It is now known to complicate the dangers of colorectal cancer more than was previously thought. Macrophages are an important part of immune system and play a positive role in immune reaction. But it has been shown that the phenotype and the function of macrophages change in the tumor microenvironment. Through their interaction with colorectal cancer cells and by releasing large quantities of cytokines, macrophages promote colorectal cancer cells by inhibiting angiogenesis and inhibit apoptosis. But the macrophages are also affected by cancer, interact with other inflammatory cells, and become immune suppressed. Thus the changes of macrophages are inseparable with colitis-associated colorectal carcinogenesis.
Carcinogenesis ; Cell Transformation, Neoplastic ; immunology ; Colitis, Ulcerative ; complications ; immunology ; pathology ; Colorectal Neoplasms ; etiology ; immunology ; pathology ; Disease Progression ; Humans ; Macrophages ; pathology

CD44 is a cell adhesion molecule with numerous isoforms created by mRNA alternative splicing. Expression of CD44 variants has been suggested to play a potential role in tumor progression and metastasis. We designed primers CD44V, CD44V6/7, CD44R1 and CD44V6-10 to analyze and compare the roles of each CD44 variants. Expressions of CD44 variants were investigated in normal colonic mucosa, the lymph nodes which was histopathologically free of cancer cell, and cancer tissues of 44 human colorectal cancer patients by RT-PCR method. The expression of CD44V was observed in 28 out of 39 (71.8%) tumors and 7 out of 11 (63.6%) N1 normal regional lymph nodes, and CD44V6/7 was observed in 28 out of 39 (71.8%) tumors and 9 out of 11 (81.8%) N1 normal regional lymph nodes. The expressions of CD44V and CD44V6/7 were most frequently observed compared with any other CD44 variants. In normal colonic mucosa, the expression of CD44 variants are low but in cancer tissue and its regional lymph node, the expression of CD44V and CD44V6/7 were significantly higher and more frequent than any other CD44 variants (p<0.05). These results suggest that CD44V and CD44V6/7 can be a molecular marker for colorectal cancer and its micrometastasis to the regional normal lymph node.
Alternative Splicing ; Antigens, CD44/genetics* ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/immunology* ; Gene Expression ; Human ; Lymph Nodes/pathology ; Lymph Nodes/immunology* ; Protein Isoforms/genetics

Clinical application of staphylococcal enterotoxin C2 (SEC2) was restricted during the cure of malignant tumor due to its side-effects. The aim of this study was to obtain SEC2 mutant, preserving the important functional sites responsible for the T-cell stimulatory activities but removing the sites responsible for emetic activity, through truncation of SEC2. It would efficiently solve the question of SEC2 side-effect. According to the results of methyl thiazol tetrazolium (MTT) assay in vitro, novel truncated SEC2 mutant (NSM) efficiently stimulated T-cell proliferation and inhibited the growth of such tumor cells as human colorectal cancer cells (Cx-1) and human breast cancer cells (MCF-7) in vitro. Activities of T cell stimulating and anti-tumor of NSM were similar to those of SEC2. According to results of animal experiments, the mutant no longer induced emetic response even if the dose was a 10-fold excess of the amount of SEC2 required. And also, NSM obviously inhibited the tumor growth in tumor-bearing mice. Therefore, we obtained novel truncated staphylococcal enterotoxin C2 mutant, which could efficiently inhibit the growth of tumor cells. It will become novel anti-tumor agents with the lowest side-effects and best treatment effects in clinic.
Animals ; Antineoplastic Agents ; adverse effects ; pharmacology ; Breast Neoplasms ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; immunology ; pathology ; Enterotoxins ; genetics ; immunology ; Humans ; Mice ; Mutant Proteins ; immunology ; Staphylococcus aureus ; immunology ; Superantigens ; immunology ; T-Lymphocytes ; immunology ; Vomiting ; prevention & control

OBJECTIVETo investigate the correlation between BRAF V600E mutation and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) therapeutic effects in metastatic colorectal cancer.

METHODSStudies were included into meta-analysis to investigate the association between BRAF V600E mutation and clinical outcome in metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

RESULTSA total of 7 studies were included in this meta-analysis. The 7 studies included 1352 patients in total, sample sizes ranged from 67 to 493. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were collected from included studies and were used to assess the strength of the relation. In patients with wild-type KRAS, the pooled odds ratio for ORR of mutant BRAF over wild-type BRAF was 0.27 (95% CI=0.10-0.70). BRAF mutation predicted a deterioration in PFS and OS in wild-type KRAS patients treated with anti-EGFR MoAbs (hazard ratio=2.78, 95% CI=1.62-4.76; hazard ratio=2.54, 95% CI=1.93-3.32).

CONCLUSIONBRAF V600E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

Antibodies, Monoclonal ; immunology ; Colorectal Neoplasms ; immunology ; pathology ; Humans ; Mutation ; Neoplasm Metastasis ; immunology ; Proto-Oncogene Proteins B-raf ; genetics ; Receptor, Epidermal Growth Factor ; immunology

OBJECTIVETo compare the immune function after laparoscopic surgery (LS) and conventional open surgery(OS) for colorectal cancer (CRC).

METHODSPubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database were systematically searched for randomized controlled trials published before August 2013 concerning the immunological difference between LS and OS. Data extraction was performed independently by two reviewers and data analysis was performed using Review Manager ver. 4.3.1.

RESULTSTwelve studies including 638 patients (307 in LS group and 331 in OS group) were eligible for analysis. Overall analysis demonstrated that no significant differences were identified for blood C-reactive protein level on postoperative days (POD) 0-1 (P=0.40), plasma lymphocyte count on POD 1-3 (P=0.92) and POD 4-7 (P=0.64), plasma CD4⁺ T cell count on POD 1-7 (P=0.63), plasma CD8⁺ T cell count on POD 4-7 (P=0.09), and plasma NK cell count POD 1-3 (P=0.34) as well as POD 4-7 (P=0.46). Data analysis also showed that a significantly lower serum level of IL-6 on POD 0-1 after LS (WMD=-25.03, 95% CI:-34.06 to -15.99, P=0.000), and a significantly higher plasma level of CD8⁺ T cell count on POD 1-3 after LS(WMD=0.05, 95% CI:0.01 to 0.08, P=0.004).

CONCLUSIONSAlthough postoperatively short-term humoral immune function trends to be better after LS for CRC compared to OS, there is no sufficient evidence to support superior preservation of global immune function after acute reactive phase.

Colorectal Neoplasms ; immunology ; surgery ; Humans ; Laparoscopy ; Laparotomy ; Randomized Controlled Trials as Topic

OBJECTIVETo compare the effect of rapid rehabilitation surgery (FTS) with the traditional operation method on postoperative immune function recovery, inflammatory reaction and the clinical efficacy in elderly patients with colorectal cancer.

METHODSA total of 144 elderly patients (older than 65 years) diagnosed as colorectal cancer in our department from February 2010 to August 2013 were prospectively enrolled in the study. According to the order of admission, patients were randomly divided into the fast track surgery group (72 cases, study group), and the traditional operation group (72 cases, control group). Preoperative and postoperative T cell subsets, inflammatory index and organ functional parameters were detected and compared.

RESULTBasal clinical data of the two groups had no significant differences (all P>0.05). Three days after operation, CD4+ and CD8+ in both groups increased compared to preoperative levels (P<0.05), while the study group had greater increasing amplitude of CD4+ (t=1.685, P=0.003), and lower CD8+(t=1.145, P=0.005) than the control group. CD4+/CD8+ increased in the study group compared to preoperation and significantly higher than that in the control group (P=0.001). Inflammatory stress indexes were significantly increased, while study group had smaller amplitude than the control group. Serum creatinine, B-natriuretic peptide and Troponin-T increased after operation, while the study group had smaller amplitude than the control group (P<0.05). The study group showed faster resumption of oral intake, quicker bowel function return, time to first defecation, hospital stay, lower incidences of nausea, vomiting, incision infection, and less cost of hospitalization. All the differences were significant (all P<0.05).

CONCLUSIONFast track surgery can effectively protect the perioperative organ function, increase postoperative immune function, decrease inflammation stress reaction, reduce perioperative morbidity of complication, improve efficacy for elderly colorectal cancer patients.

Aged ; Colorectal Neoplasms ; surgery ; Defecation ; Humans ; Inflammation ; immunology ; Length of Stay ; Postoperative Period

OBJECTIVETo compare the effect of laparoscopic radical operation and open operation on systemic immunity in patients with colorectal cancer.

METHODSSixty patients with colorectal cancer were randomly divided into laparoscopic and open operation groups from March 2004 to December 2004, each group had 30 cases. CRP, IgA, IgM, IgG, CD3 (+) cells, CD4 (+) cells, CD8 (+) cells, NK cells, CD4 (+) CD5RA (+) cells, CD4 (+) CD45RO (+) cells and lymphocytes in peripheral blood were counted and compared on the 1st day before operation, 3rd and 7th day after operation.

RESULTSThe two groups were comparable as for age, tumor location and stages. In open operation group, lymphocyte counts were (1.09+/- 0.29) x 10(9)/L, CD4 (+) cell (0.54 +/- 0.14) x 10(9)/L, CD8 (+) cell (0.31 +/- 0.08) x 10(9)/L, CD4 (+) CD45RO (+) (61.1+/- 8.9)%, and IgM level (136.9+/- 52.8) IU/ml, IgG (115.2 +/- 45.7) IU/ml on the 3rd day after operation, CD8 (+) cell counts were (0.32 +/- 0.09) x 10 (9)/L, CD4 (+) CD45RO (+) cell (63.2 +/- 9.1)% on the 7th day after operation, were all significantly lower than those on the 1st day before operation respectively(P< 0.05, P< 0.01). In laparoscopic operation group, the decreases of such parameters except CD4 (+) CD45RO (+) cell (62.7 +/- 12.5)% were not obvious on the 3rd day after operation. There were significant difference in lymphocyte counts (1.29 +/- 0.37) x 10( 9 )/L, IgM (164.5 +/- 48.2) IU/ml and CD8 (+) cell counts (0.38 +/- 0.09) x 10 (9) /L on the 3rd day after operation between two groups (P< 0.05).

CONCLUSIONCompared with open radical operation, laparoscopic radical operation has predominance in protecting systemic immunity to treat colorectal carcinoma.

Aged ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; immunology ; Colorectal Neoplasms ; immunology ; surgery ; Female ; Humans ; Killer Cells, Natural ; immunology ; Laparoscopy ; Lymphocyte Count ; Male ; Middle Aged