***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Regulatory T cells ( T(reg ) ) inhibit the generation of host-versus-tumor immunity via suppression of tumor-specific effector T-cell responses and development of immune tolerance to neoplastic cells . The transcription factor forkhead box P3 ( FOXP3 ) is an intracellular key molecule for T(reg ) development and function and is considered to represent the most specific T(reg ) cell marker . The aim of this study was to analyze the frequency and prognostic impact of tumor-infiltrating FOXP3(+ ) T(reg ) in colorectal cancer ( CRC ) stratified by mismatch-repair ( MMR ) status . Using the tissue microarray technique , 1,420 tumor sample s were immunohistochemically stained for FOXP3 and stratified into 1,197 MMR-proficient and 223 MMR-deficient CRCs . Additionally , the 1,197 MMR-proficient CRCs were r and omized into 2 subgroups ( Test Groups 1 and 2 ; n = 613 and 584 , respectively ) . In both MMR-proficient CRC subgroups high frequency tumor-infiltrating FOXP3(+ ) T(reg ) was associated with early T stage ( p = 0.001 and < 0.001 ) , tumor location ( p = 0.01 and 0.045 ) and increased 5-year survival rate ( p = 0.004 and < 0.001 ) , whereas in MMR-deficient CRCs an association between FOXP3(+ ) T(reg ) and absence of lymph node involvement ( p = 0.023 ) , absence of vascular invasion ( p = 0.023 ) and improved 5-year survival rate ( p = 0.029 ) could be detected . In a multivariable analysis including age , gender , T stage , N stage , tumor grade , vascular invasion , and tumor border configuration , a high FOXP3(+ ) T(reg ) frequency was an independent prognostic factor in both MMR-proficient CRC subsets ( p = 0.019 and p = 0.007 ) , but not in the MMR-deficient CRCs ( p = 0.13 ) . Therefore , high frequency of tumor-infiltrating FOXP3(+ ) T(reg ) is associated with early T stage and independently predicts improved disease-specific survival in MMR-proficient CRC patients Breast carcinomas are often infiltrated by inflammatory cells , particularly macrophages and T lymphocytes , but the significance of these cells remains unclear . One possible role of these inflammatory cells is that they represent a cell-mediated immune response against the carcinoma . CD8(+ ) lymphocytes are a known crucial component of cell-mediated immunity . The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8(+ ) cytotoxic lymphocytes in breast cancer .  Tumor-infiltrating CD8(+ ) lymphocytes were assessed by immunohistochemical staining of tissue microarray cores from 1,334 unselected breast tumors from patients with long-term follow-up . The number of CD8(+ ) T cells was counted in tumor nests ( intratumoral ) , in stroma adjacent to tumor cells , and in stroma distant to tumor cells , and their relationship with clinical outcome was determined . The total number of CD8(+ ) cells was positively correlated with tumor grade ( r(s ) = 0.20 ; P < .001 ) and inversely correlated with patient 's age at diagnosis , estrogen receptor-alpha ( ER-α ) , and progesterone receptor ( PgR ) expression ( Mann-Whitney U test , P < .001 ) . The total patient cohort was r and omly divided into two separate training and validation sets before performing univariate survival analysis . Total number and distant stromal CD8(+ ) lymphocytes were associated with better patient survival ( P = .041 and P < .001 , respectively ) in the training set . In multivariate analysis , total CD8(+ ) T-cell count was an independent prognostic factor in both training and validation sets . These results suggest that tumor-infiltrating CD8(+ ) T lymphocytes have antitumor activity as judged by their favorable effect on patients ' survival and could potentially be exploited in the treatment of breast cancer Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies , like GOLFIG chemoimmunotherapy ( gemcitabine , oxaliplatin , 5-fluorouracil/folinic acid , granulocyte macrophage colony-stimulating factor , and aldesleukine ) , that result ed a safe and very active regimen . Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs , increase of central memory T cells , and decrease of regulatory T cells ( Treg ) in the peripheral blood . We thus investigated a potential correlation between the Treg tumor infiltration at diagnosis and the clinical outcome in a current r and omized phase 3 trial aim ed to compare the GOLFIG regimen with the st and ard FOLFOX chemotherapy ( GOLFIG-2 ) . An immunohistochemistry study was carried out to quantify the infiltration of Treg/FoxP3 + T lymphocytes in tumor sample s of 57 patients enrolled in the GOLFIG-2 trial .  Treg tumor infiltration scores were correlated with overall survival , treatment-relative survival , and progression-free survival ( PFS ) . Higher Treg tumor infiltration scores were associated with a better prognosis in the whole series ( Treg high score vs. low score : overall survival = mean 43.2 mo vs. 28.6 mo , P=0.0005 ) and a better outcome after treatment ( Treg high score vs. low score : PFS = mean 15.8 mo vs. 8.8 mo , P=0.0009 ; treatment-relative survival = mean 23.1 mo vs. 18.2 mo , P=0.004 ) . PFS was significantly longer in GOLFIG high versus all other subgroups ( mean 18.1 mo vs. 9.9 mo , P=0.01 ) . Our results suggest that a higher FoxP3 + T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours , but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification . In the present study , the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed . Intra-operative tumour tissue sample s from 584 patients undergoing elective surgery for colorectal cancer were included . None of the patients received pre- or post-operative adjuvant chemotherapy . Tissue blocks were cut from the periphery of the tumours and embedded in paraffin . All blocks included both tumour tissue and normal bowel tissue . Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope , which allowed semi-automated quantification of cells within a fixed area . Total white cells and individual counts of eosinophils , neutrophils , mast cells , lymphocytes , and plasma cells were evaluated in every tumour specimen . Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival . The median observation period was 61 ( 49 - 75 ) months . In a multivariate analysis including Dukes ' stage , gender , age , peri-operative blood transfusion , tumour location , and counts of specific inflammatory cells , only advanced Dukes ' stage ( p < 0.0001 ) , high age ( p=0.0003 ) , and tumour location in the rectum predicted poor survival , while high counts of eosinophils ( p=0.006 ) and mast cells ( p=0.02 ) predicted good survival . Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer . Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth Purpose : An efficient adaptive immunity is critical for a longer survival in cancer . We investigated the prognostic value of tumor infiltration by CD8 + T cells expressing the chemokine-receptor-7 ( Tccr7 ) and the correlation between tumor infiltration by Tccr7 and regulatory CD4+FoxP3 + T cells ( Treg ) in 76 metastatic colorectal cancer ( mCRC ) patients enrolled in a phase III trial . Experimental Design : Tccr7 and Treg cell infiltration in tumor sample s was quantified by immunohistochemistry . The correlation among Tccr7 , Treg tumor infiltration , and patients ' outcome was evaluated . Results : High Tccr7 tumor infiltration was predictive of prolonged OS [ high vs. low Tccr7 score : median 38 months ( 95 % CI : 24.5–51.4 ) vs. 20 months ( 95 % CI : 11.4–28.5 ) ; HR = 0.48 ( 95 % CI : 0.24–0.96 ) ; P = 0.03 ] and prolonged progression-free survival [ PFS ; high vs. low Tccr7 score : median 12 months ( 95 % CI : 7.7–16.2 ) vs. 7 months ( 95 % CI : 5.2–8.7 ) ; HR = 0.54 ( 95 % CI : 0.28–1.01 ) ; P = 0.01 ] after front-line chemotherapy . Regression analysis did not show correlation between Tccr7 and Treg infiltration levels . However , the cluster of patients showing concomitant high infiltration by both Tccr7 and Treg disclosed a favorable outcome [ double high vs. double low tumor infiltration score : median OS = 35 months ( 95 % CI : 20.8–49.1 ) vs. 17 months ( 95 % CI : 4.6–29.3 ) ; HR = 0.32 ( 95 % CI : 0.12–0.87 ) ; P = 0.02 and median PFS = 11 months ( 95 % CI : 9.4–12.5 ) vs. 5 months ( 95 % CI : 2.2–7.7 ) ; HR = 0.43 ( 95 % CI : 0.17–1.06 ) ; P = 0.01 ] . Conclusions : High Tccr7 tumor infiltration score is a favorable prognostic factor for mCRC . Our findings underline the relevance of microenvironment-related immunologic events for patient outcome . Clin Cancer Res ; 18(3 ) ; 850–7 . © 2011 AACR Purpose : Host immune response to tumor may be an important prognostic factor for colon cancer patients . However , little is known on prognostic significance of histopathologic lymphoid reaction to tumor , independent of the number of lymph nodes examined and tumoral molecular alterations , including microsatellite instability ( MSI ) and the CpG isl and methylator phenotype ( CIMP ) , both of which are associated with lymphocytic reaction and clinical outcome . Experimental Design : Using 843 colorectal cancer patients in two independent prospect i ve cohorts , we examined patient prognosis in relation to four components of lymphocytic reaction ( i.e. , Crohn's-like reaction , peritumoral reaction , intratumoral perigl and ular reaction , and tumor-infiltrating lymphocytes ) and overall lymphocytic score ( 0 - 12 ) . CIMP was determined using eight markers including CACNA1 G , CDKN2A ( p16 ) , CRABP1 , IGF2 , MLH1 , NEUROG1 , RUNX3 , and SOCS1 . Cox proportional hazard models computed hazard ratio for mortality , adjusted for covariates including tumor stage , body mass index , lymph node count , KRAS , BRAF , p53 , cyclooxygenase-2 ( PTGS2 ) , MSI , CIMP , and LINE-1 methylation . Results : Increasing overall lymphocytic reaction score including tumor-infiltrating lymphocytes was associated with a significant improvement in colorectal cancer – specific and overall survival ( log-rank P < 0.003 ) . These findings remained significant ( adjusted hazard ratio estimates , 0.49 - 0.71 ; Ptrend < 0.009 ) in multivariate models that adjusted for covariates , including body mass index , MSI , CIMP , LINE-1 hypomethylation , and cyclooxygenase-2 . The beneficial effect of tumoral lymphocytic reaction was consistent across strata of clinical , pathologic , and molecular characteristics . Conclusions : Lymphocytic reactions to tumor were associated with improved prognosis  among colorectal cancer patients , independent of lymph node count and other clinical , pathologic , and molecular characteristics . ( Clin Cancer Res 2009;15(20):6412–20 PURPOSE To 
    Output:
    
Stratification by location and T lymphocyte subset indicated that in the tumour centre , CD3 + , CD8 + and FoxP3 + infiltrates were not statistically significant prognostic markers for OS or CS .
In the tumour stroma , high CD8 + , but not CD3 + or FoxP3 + cell infiltrates indicated increased OS .
Furthermore , high CD3 + cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS ; and high CCR7 + infiltrate was also indicated increased OS .
Conclusion : Overall , high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC .