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

Adoptive cell transfer of tumor-infiltrating lymphocyte (TIL) has resulted in clear and reproducible responses in a substantial percentage (approximately 50%) of patients with metastatic melanoma. The availability of tumor reactive TIL limits the use of adoptive cell transfer for the treatment of most non-melanoma cancer patients. Recent report indicated that adoptive transfer of T lymphocytes genetically modified with T-cell receptor (TCR) against a tumor antigen resulted in objective response in melanoma patients, thus shedding light on the use of this strategy for the treatment of common epithelial cancers beyond melanoma. In this review, the current status and potential use of genetic modification in the adoptive immunotherapy of cancer patients are be discussed.
Genetic Therapy ; methods ; Humans ; Immunotherapy, Adoptive ; methods ; trends ; Lymphocytes, Tumor-Infiltrating ; immunology ; transplantation ; Neoplasms ; therapy

Breast cancer is a heterogeneous disease. The formation and progression of tumor and the sensitivity to treatment differs from patient to patient. In addition to the widely used molecular subtype, novel markers are needed to better personalize the treatment of breast cancer. Tumor infiltrating lymphocyte (TIL) have been consistently documented in breast cancer lesions especially in triple negative and human epidermal growth factor receptor-2 positive breast cancer. Several clinical trials have revealed that TIL are associated with prognosis and can predict therapeutic efficacy of special therapy. TIL could be divided to different subtypes including CD8 + TIL, CD4 + TIL, cytotoxic T lymphocyte-associated antigen-4 + TIL, programmed death-1 + TIL. They play different roles in the process of anti-tumor immunity and can predict different prognosis. Screening out special TIL subtype which is well associated with prognosis and therapeutic efficacy and developing targeting immunotherapy can help to improve outcomes of breast cancer patients.
Breast Neoplasms ; diagnosis ; immunology ; Humans ; Lymphocytes, Tumor-Infiltrating ; classification ; cytology ; Prognosis

OBJECTIVETo explore the adoptive immunotherapy effect of peripheral gammadeltaT cells in pancreatic cancer nude mice model.

METHODSThirty BALB/c nude mice were inoculated subcutaneously 5 x 10(5) Cap-1 cells to regularly developed hypodermal tumors, and then divided into 3 groups randomly, gammadeltaT cells, alphabetaT cells and control group. 2.5 x 10(6) gammadeltaT cells or alphabetaT cells or 100 microl RPMI-1640 were respectively injected into abdominal cavity of mice, combined with 10(4) U rhIL-2 for 3 times. Tumor volume, the survival rate and anti-carcinogenic rate of three groups were compared.

RESULTSEight control nude mice developed hypodermal tumors, which progressively increased in size, and animals had a mean survival of 88 d. Nine nude mice in gammadeltaT cells group and eight in alphabetaT cells group developed tumors (P > 0.05). Tumor growth was arrested and tumor size was reduced remarkably in gammadeltaT cells group. Mean survival was increased to 113 d with less rate of tumor metastasis and more cases of tumor necrosis in gammadeltaT cells group when compared with alphabetaT cells group and controls.

CONCLUSIONSThe anti-tumor effects of gammadeltaT cells against pancreatic cancer are better than those of alphabetaT cells and control groups, and might be promising in the adoptive immunotherapy of pancreatic cancer.

Animals ; Humans ; Immunotherapy, Adoptive ; methods ; Lymphocytes, Tumor-Infiltrating ; immunology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pancreatic Neoplasms ; immunology ; pathology ; therapy ; T-Lymphocytes ; immunology

OBJECTIVETo study the expression of Mucin1 gene and tumor infiltrating dendritic cells(TIDC) in the tissues of benign prostatic hyperplasia (BPH) and prostate cancer.

METHODSMucin1 and TIDC were detected in 20 specimens of BPH and 30 specimens of prostate cancer by immunohistochemistry SP method.

RESULTSMUC1 expressed in both prostate cancer and BPH. The staining patterns were significantly associated with tumor pathological grade (P < 0.001). The number of TIDC was negatively correlated with tumor pathological grade, the higher the grade, the smaller the number of TIDC (P < 0.001).

CONCLUSIONSThe expression pattern of MUC1 and the number of TIDC could be considered as useful markers to evaluate the malignant degree and prognosis of prostate cancer. The decrease of TIDC plays an important role in tumor immune evasion and immune tolerance. Highly expressed MUC1 could lead to the failure of hormonal treatment for prostate cancer, and contribute much to tumor infiltration and metastasis.

Antigens, Neoplasm ; biosynthesis ; Dendritic Cells ; immunology ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Mucin-1 ; Mucins ; biosynthesis ; Prostatic Hyperplasia ; immunology ; metabolism ; pathology ; Prostatic Neoplasms ; immunology ; metabolism ; pathology

OBJECTIVETo explore the clinical significances of dendritic cells and lymphocytes infiltration in hepatocellular carcinoma (HCC) tissue.

METHODSClinicopathological data were collected from 44 patients with HCC who had under/gone curative tumor resection in our hospital. Immunohistochemical staining was used to detect the infiltration of dendritic cells in the tumor tissue, and lymphocytes infiltration was assessed simultaneously. The correlation between the infiltration of dendritic cells and lymphocytes and postoperative tumor recurrence and survival rate was analyzed.

RESULTSTumor recurrence was markedly late in patients with dendritic cells count >/= 20 and positive lymphocytes infiltration (group A, n = 17) as compared with those who did not meet both criteria simultaneously (group B, n = 27), with a median interval of 21.6 months for group A and 4.1 months for group B (U value = 105.5, P = 0.009). The 1-, 3-, 4-year survival rates were significantly greater in group A than in group B; they were 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs. 23.0%, respectively (Log rank = 7.68, P < 0.01).

CONCLUSIONThe infiltration of dendritic cells and lymphocytes in HCC tissue, as an independent prognostic factor, was closely related to postoperative prognosis.

Adult ; Aged ; Carcinoma, Hepatocellular ; immunology ; Cell Count ; Dendritic Cells ; immunology ; Female ; Humans ; Liver Neoplasms ; immunology ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Neutrophil Infiltration ; Prognosis ; Recurrence ; Secondary Prevention

OBJECTIVETo investigate the therapeutic effect of sequential intratumoral injection of xenogeneic antigens in immunized tumor-bearing mice.

METHODSSequential intratumoral injection of the xenoantigens was performed in immunized mice bearing S180 tumor. The tumor size changes were observed, and the tumor-infiltrating lymphocytes (TIL) including CD3+CD4+T, CD3+CD8+T, and CD3+CD4+CD25+T lymphocytes were counted with flow cytometry. The concentrations of IL-2 and TNF-alpha in the tumor was measured using ELISA.

RESULTSNo significant difference was found in the number of CD3+T lymphocytes in the TILs between different groups. After the immunotherapy, the percentages of CD3+CD4+T, CD3+CD8+T and CD3+CD4+CD25+T lymphocytes were 54%, 22% and 2.91%, respectively, with the CD4+/CD8+ ratio of 2.49, significantly different from that in the control group (P<0.05). The concentrations of IL-2 and TNF-alpha were 100.61 pg/ml and 54.114 pg/ml, respectively, significantly different from those in the control group (P<0.05).

CONCLUSIONSequential intratumoral injection of heteragenetic antigena can significantly increase the amount of effector cells and cytokines in the micro-environment of the tumor, and decrease the expression of T regulatory.

Animals ; Antigens, Heterophile ; immunology ; CD4-CD8 Ratio ; Female ; Immunotherapy ; methods ; Lymphocytes, Tumor-Infiltrating ; cytology ; Male ; Mice ; Random Allocation ; Sarcoma 180 ; immunology ; therapy ; Streptococcus ; immunology

BACKGROUNDAltered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

METHODSParaffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

RESULTSThe data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

CONCLUSIONSThe levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

CD3 Complex ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Lung Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; metabolism ; Male ; Prognosis

OBJECTIVETo assess the prognostic value of CD20(+) tumor-infiltrating lymphocytes (TILs) in early-stage breast cancer.

METHODSParaffin sections were collected from 130 cases of stage I-III breast cancer undergoing surgery between January, 2000 and December, 2002 in our hospital. Immunohistochemistry was used to analyze mesenchymal CD20(+) TILs infiltration in the tumor and evaluate its association with the density of CD4(+) and CD8(+) TILs. The association of CD20(+) TILs was evaluated with the histopathologic features, overall survival (OS), distant disease-free survival (DDFS), and disease-free survival (DFS) of the patients.

RESULTSAggregations of CD20(+) lymphocytes were observed in 37.69% (49/130) of the cases. CD3(+) T cells were found to aggregate around CD20(+) B cell aggregations to form lymphoid follicle-like structures. The aggregations of CD20(+) TILs were positively correlated with the densities of mesenchymal CD8+ and CD4(+) TILs. Overall, CD20(+) TIL aggregations were not significantly correlated with the outcomes of the patients, but multivariate COX regressions suggested that CD20(+) TIL aggregations were positively correlated with DDFS (HR=0.251, 95% CI=0.071-0.894, P=0.033) and OS (HR=0.325, 95% CI=0.103-1.028, P=0.056) in hormone receptor-negative patients but not in the positive patients. Further analysis suggested that post-operative adjuvant endocrine therapy significantly improved the OS of patients positive for hormone receptors without CD20(+) TIL aggregations (P=0.001).

CONCLUSIONThe long-term therapeutic effects of adjuvant endocrine therapy are correlated with CD20(+) TIL aggregations to affect prognostic value of CD20(+) TIL aggregations in early-stage breast cancer patients.

Antigens, CD20 ; metabolism ; B-Lymphocytes ; cytology ; Breast Neoplasms ; immunology ; pathology ; Disease-Free Survival ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating ; cytology ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Survival Rate

BACKGROUNDImmune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC.

METHODSThirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations.

RESULTSCompared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05).

CONCLUSIONSThese observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.

Adult ; Aged ; Carcinoma, Renal Cell ; immunology ; metabolism ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Neovascularization, Pathologic ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; immunology