Prognostic impact of tumor-associated B cells and plasma cells in colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 587-587
Author(s):  
Jonna Berntsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom
Keyword(s):  
Colorectal Cancer ◽  
B Cell ◽  
Immune Cell ◽  
Multivariable Analysis ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Cd20 Expression ◽  
Incident Cases ◽  
The Impact

587 Background: Multiple studies have described associations between infiltrating immune cells, prognosis and treatment response in cancer. However, the clinical relevance has most often been attributed to the T-cell linage, whereas the humoral immune response is less investigated. In colorectal cancer (CRC), accumulation of CD20-positive B lymphocytes at the advancing margin of metastatic CRC has been demonstrated to correlate with prolonged survival. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in colorectal cancer (CRC). Methods: Immunohistochemical expression of CD20 and CD138 in was analyzed in tissue microarrays with tumors from 557 incident cases of CRC from the Malmö Diet and Cancer Study, a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20 and CD138 expression on 5-year overall survival (OS). Results: CD20 expression could be evaluated in 549 (98.6 %) cases and CD38 in 534 (95.9 %) cases. CD20 expression correlated significantly with both immune cell-specific and tumor-specific expression of CD138 (p < 0.001 and p = 0.001, respectively). Furthermore, immune cell-specific CD20 and CD138 expression as well as tumor-specific CD138 expression correlated significantly with lower T-stage (p < 0.001, p < 0.001 and p = 0.002, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.66, 95 % CI 0.50-0.86), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.65; 95% CI 0.48-0.90). Neither immune cell nor tumor cell-specific CD138 expression was significantly associated with prognosis. Conclusions: Our results demonstrate that increased B cell infiltration in CRC is an independent factor of improved prognosis. Moreover, the study provides a first demonstration of the expression and clinicopathological correlates of immune cell-specific CD138 expression in CRC, thus providing a further characterization of the immune landscape in this type of cancer.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

Impact of M1a and M1b staging in patients (pts) with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3590-3590 ◽  
Author(s):  
Hagen F. Kennecke ◽  
Jason Yu ◽  
Sharlene Gill ◽  
Winson Y. Cheung ◽  
Charles Davic Blanke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
7Th Edition ◽  
The Impact

3590 Background: In 2009, pts with M1 colorectal cancer were divided into two subsets for the American Joint Committee on Cancer (AJCC) 7th edition. Pts with metastases (mets) confined to one organ or site at initial diagnosis became stage M1a while multiple sites or peritoneal mets became M1b. The objectives of the study are to evaluate the impact of site of mets and M1a/b staging among pts with M1 colorectal cancer. Methods: All pts referred to the BC Cancer Agency from 1999-2007 with newly diagnosed M1 colon or rectal cancer were included. Demographic, treatment, and outcome data were prospectively collected. The prognostic impact of individual sites of mets was assessed by hazard ratio estimates from univariate Cox models. Multivariable Cox proportional-hazards models were used to determine variables associated with overall survival in the entire cohort and in those undergoing resection of their primary tumor. Results: 2,049 pts with M1 disease were included. Median age was 66 years; 71% had colonic origin; 70% had their primary tumor resected; and 69% received chemotherapy. In univariate analysis, solitary mets were associated with improved survival. In multivariable analysis, M1a/b status still had significant prognostic effect. The effect remained significant in the subgroup analysis of pts with resected primary tumors when histology, T and N stage were included. Conclusions: Pts with solitary mets, including peritoneum, have superior overall survival as compared to those with multiple sites of mets. AJCC 7th edition staging that includes M1a/b provides significant prognostic information and should be considered in clinical practice and trials of pts with M1 disease who otherwise have few prognostic factors. [Table: see text]

scholarly journals The Immune Phenotype of Isolated Lymphoid Structures in Non-Tumorous Colon Mucosa Encrypts the Information on Pathobiology of Metastatic Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3117
Author(s):  
Felicitas Mungenast ◽  
Anastasia Meshcheryakova ◽  
Andrea Beer ◽  
Martina Salzmann ◽  
Dietmar Tamandl ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
B Cell ◽  
Lymphoid Tissue ◽  
Immune Cell ◽  
Metastatic Tumor ◽  
Risk Groups ◽  
Colon Tissue ◽  
Immune Phenotype ◽  
Lymphoid Structures ◽  
The Impact

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.

The difference in prognostic value of tumour-infiltrating T cells according to adjuvant chemotherapy in radiochemonaïve gastroesophageal cancer.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 41-41
Author(s):  
Maria Christina Svensson ◽  
Jonna Berntsson ◽  
Charlotta Hedner ◽  
David Borg ◽  
Bjorn Nodin ◽  
...  
Keyword(s):  
T Cells ◽  
Adjuvant Chemotherapy ◽  
Gastric Adenocarcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Prognostic Impact ◽  
Prognostic Information ◽  
Cox Regression Analysis ◽  
The Impact

41 Background: Several studies have demonstrated a beneficial prognostic impact of tumour-infiltrating lymphocytes (TILs) in oesophageal and gastric adenocarcinoma, but whether this association differs according to adjuvant chemotherapy has not been reported. Herein, we examined the prognostic impact of different TIL subsets according to adjuvant chemotherapy in these cancer types. Methods: Immunohistochemistry was applied to assess the density of T cells (CD3+, CD8+, FoxP3+) and natural killer (NK)/T cells (CD56+) in radiochemonaïve tumors from a consecutive cohort of 174 patients with resected oesophageal or gastric adenocarcinoma. Cox proportional hazard’s modelling was applied to examine the impact of the investigated markers on time to recurrence (TTR) and overall survival (OS). Results: Dense infiltration of CD3+, CD8+, and FoxP3+ cells were all associated with a significantly prolonged TTR in univariable Cox regression analysis (hazard ratio[HR] = 0.57; 95% confidence interval [CI] 0.37-0.89; HR = 0.31, 95% CI 0.13-0.77, and HR = 0.44, 95% CI 0.28-0.68). This association remained significant for CD8+ and FoxP3+ cells in multivariable analysis, adjusted for age, tumour location, TNM stage, differentiation grade, resection margin and adjuvant chemotherapy ( HR = 0.30, 95% CI 0.11-0.77, and HR = 0.52, 95% CI 0.32-0.84), and borderline significant for CD3+ cells (HR = 0.63, 95% CI 0.39-1.02). Similar associations were observed for all markers in relation to OS. Notably, analysis in strata according to adjuvant chemotherapy revealed that none of the investigated lymphocyte subsets carried prognostic information in patients having received treatment (n = 13; 7.5%), with a significant treatment interaction between CD3+ and CD8+ cells and adjuvant chemotherapy (pinteraction0.035 and 0.021). Conclusions: These results confirm the prognostic value of a high density of TILs in gastroesophageal adenocarcinoma, but also indicate that adjuvant chemotherapy is only beneficial in patients with tumors displaying a low density of TILs. These results are of potential clinical relevance and need to be confirmed in additional, preferentially randomized, studies.

Increasing use of neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC): Prognostic impact of non-standard of care (SOC) regimens.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4532-4532 ◽  
Author(s):  
Yaw A. Nyame ◽  
Sarah K Holt ◽  
Brian Winters ◽  
Sarah P. Psutka ◽  
Atreya Dash ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Logistic Regression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Population Based ◽  
Competing Risk ◽  
Oncologic Outcomes ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
The Impact

4532 Background: Cisplatin-based NAC can prolong overall survival (OS) in patients (pts) with MIBC. Utilization of NAC has increased to about 20% of pts with MIBC over the last decade. We evaluated NAC utilization with and without SOC cisplatin-based combination regimens and oncologic outcomes using registry data. Methods: This is a population-based analysis of linked SEER-Medicare data (2004-2011). We identified 4534 pts with MIBC (cT2-4N0-1) undergoing radical cystectomy (RC). Based on pharmacy records data, pts were stratified into 3 groups: SOC, non-SOC, and immediate cystectomy (IC). We used descriptive statistics to compare groups, and multivariate logistic regression to define factors associated with receiving SOC NAC. Competing risk bladder cancer-specific mortality (BCSM) incidence curves were generated and KM analysis was used to assess OS from time of RC. The impact of NAC on OS was evaluated with Cox regression analysis. Results: 694 (15.3%) pts received NAC, increasing from 11% in 2004 to 24.8% in 2011, with 345 (50%) receiving non-SOC, e.g. gemcitabine/carboplatin (49.3%), gemcitabine alone (21.2%), carboplatin alone (14.8%), cisplatin alone (8.4%), and methotrexate/vinblastine/ adriamycin/carboplatin (0.8%). On logistic regression, increasing age (OR 0.91, 95%CI 0.88 – 0.94, p < 0.0001), Hispanic/Latin ethnicity (OR 0.49, 95%CI 0.22 – 1.10, p = 0.08), and ≥moderate renal dysfunction (OR 0.20, 95%CI 0.08 – 0.51, p < 0.001) were associated with lower odds of SOC NAC. Non-SOC NAC was associated with higher BCSM (competing risk) and lower OS (KM) vs. IC and SOC NAC. On multivariable analysis, non-SOC NAC was associated with higher risk of BCSM (HR 1.35, 95%CI 1.06 – 1.72, p = 0.01) and lower OS (HR 1.38, 95%CI 1.11 – 1.70, p = 0.003) vs. SOC NAC. Conclusions: About 50% of pts receiving NAC were not treated with SOC regimens. Non-SOC NAC was associated with higher bladder cancer death risk. This stresses the role of SOC NAC ideally in a multidisciplinary expert setting, as well as the need for timely RC and neoadjuvant clinical trials, including cisplatin-ineligible pts.

scholarly journals Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 3410-3425
Author(s):  
Xiangzhou Tan ◽  
Linfeng Mao ◽  
Changhao Huang ◽  
Weimin Yang ◽  
Jianping Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Networks ◽  
Immune Cell ◽  
Comprehensive Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

B-cell lymphoma/leukaemia 10 and angiotensin II-induced kidney injury

2019 ◽  
Author(s):  
Lajos Markó ◽  
Joon-Keun Park ◽  
Norbert Henke ◽  
Song Rong ◽  
András Balogh ◽  
...  
Keyword(s):  
B Cell ◽  
Renal Damage ◽  
Cardiac Fibrosis ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
Kidney Injury ◽  
B Cell Lymphoma ◽  
Cell Infiltration ◽  
Tubular Damage ◽  
Ang Ii

Abstract Aims B-cell lymphoma/leukaemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II, and antigen-dependent immune-cell activation to nuclear factor kappa-B signalling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodelling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage. Methods and results Bcl10 knockout mice (Bcl10 KO) and wild-type (WT) controls were given 1% NaCl in the drinking water and Ang II (1.44 mg/kg/day) for 14 days. Additionally, Bcl10 KO or WT kidneys were transplanted onto WT mice that were challenged by the same protocol for 7 days. Kidneys of Ang II-treated Bcl10 KO mice developed less fibrosis and showed fewer infiltrating cells. Nevertheless, neutrophil gelatinase-associated lipocalin (Ngal) and kidney injury molecule (Kim)1 expression was higher in the kidneys of Ang II-treated Bcl10 KO mice, indicating exacerbated tubular damage. Furthermore, albuminuria was significantly higher in Ang II-treated Bcl10 KO mice accompanied by reduced glomerular nephrin expression and podocyte number. Ang II-treated WT mice transplanted with Bcl10 KO kidney showed more albuminuria and renal Ngal, compared to WT- > WT kidney-transplanted mice, as well as lower podocyte number but similar fibrosis and cell infiltration. Interestingly, mice lacking Bcl10 in the kidney exhibited less Ang II-induced cardiac hypertrophy than controls. Conclusion Bcl10 has multi-faceted actions in Ang II-induced renal damage. On the one hand, global Bcl10 deficiency ameliorates renal fibrosis and cell infiltration; on the other hand, lack of renal Bcl10 aggravates albuminuria and podocyte damage. These data suggest that Bcl10 maintains podocyte integrity and renal function.

scholarly journals Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration

2018 ◽  
Vol 115 (50) ◽  
pp. E11701-E11710 ◽  
Author(s):  
Yoong Wearn Lim ◽  
Haiyin Chen-Harris ◽  
Oleg Mayba ◽  
Steve Lianoglou ◽  
Arthur Wuster ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Immunotherapy ◽  
Genetic Variants ◽  
Immune Cell ◽  
Response To Therapy ◽  
Cell Infiltration ◽  
Cancer Type ◽  
Immune Cell Infiltration ◽  
Durable Response ◽  
The Impact

Cancer immunotherapy has emerged as an effective therapy in a variety of cancers. However, a key challenge in the field is that only a subset of patients who receive immunotherapy exhibit durable response. It has been hypothesized that host genetics influences the inherent immune profiles of patients and may underlie their differential response to immunotherapy. Herein, we systematically determined the association of common germline genetic variants with gene expression and immune cell infiltration of the tumor. We identified 64,094 expression quantitative trait loci (eQTLs) that associated with 18,210 genes (eGenes) across 24 human cancers. Overall, eGenes were enriched for their being involved in immune processes, suggesting that expression of immune genes can be shaped by hereditary genetic variants. We identified the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene as a pan-cancer type eGene whose expression levels stratified overall survival in a subset of patients with bladder cancer receiving anti–PD-L1 (atezolizumab) therapy. Finally, we identified 103 gene signature QTLs (gsQTLs) that were associated with predicted immune cell abundance within the tumor microenvironment. Our findings highlight the impact of germline SNPs on cancer-immune phenotypes and response to therapy; and these analyses provide a resource for integration of germline genetics as a component of personalized cancer immunotherapy.

scholarly journals TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling

2018 ◽  
Vol 116 (1) ◽  
pp. 211-216 ◽  
Author(s):  
Bochra Zidi ◽  
Christelle Vincent-Fabert ◽  
Laurent Pouyet ◽  
Marion Seillier ◽  
Amelle Vandevelde ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
B Lymphopoiesis ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
The Impact ◽  
Deficient Mice

Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.

Abstract P207: Incidence of Hypertension in Colombia Similar to That Observed Decades Ago in Developed Countries: An Observation From the Chicamocha Cohort Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Juan C Villar ◽  
Luz X Martínez ◽  
Yeny Z Castellanos ◽  
Skarlet M Vásquez ◽  
Víctor M Herrera
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Incidence Rate ◽  
Latin American ◽  
Cox Regression ◽  
Population Attributable Fraction ◽  
Developed Countries ◽  
Cox Regression Analysis ◽  
Incident Cases ◽  
The Impact

Background: Overweight is a modifiable risk factor for high blood pressure (BP). Despite the increasing prevalence of both conditions in the Latin American population, there are no estimates of either the incidence of hypertension or the impact of overweight on it that inform the design and evaluation of individual and community-based preventive interventions in the region. Methods: We conducted a prospective cohort study in a sample of normotensive, blood donors from Bucaramanga, Colombia, who were free of transfusion-transmitted infectious and cardiovascular diseases at baseline. Participants were re-evaluated after a median follow-up of 12 years to determine the incidence of hypertension defined as: 1) Self-reported diagnosis with evidence of pharmacological treatment; 2) Systolic BP >140 mmHg or diastolic BP >90 mmHg (average of two measures in seated position); or 3) Current systolic/diastolic BP >120/80 mmHg with evidence of increments >10/5 mmHg from baseline. We estimated crude incidence rates of hypertension and age- and sex-adjusted hazard ratios (HRs) for baseline overweight (body mass index ≥25 kg/m2) using Cox regression analysis. The population attributable fraction (PAF) for overweight was also assessed. Results: We followed 594 participants (baseline mean age = 38.0 years; 64% male; adherence rate = 78%) at risk of hypertension among which we observed 164 incident cases: Cumulative incidence of 27.6%; incidence rate of 23.4 cases per 1,000 person-years. Incidence rate was similar in men and women (23.4 vs. 23.2 per 1,000 person-years; p>0.05) and tended to increase with age (17.4, 21.2, and 27.8 per 1,000 person-years among participants <30, 30-39, and ≥40 years old, respectively; p>0.05). Participants with overweight at baseline had twice the risk of developing hypertension than participants with normal weight (adjusted-HR = 2.00, 95%CI: 1.11, 3.61). The estimated PAF was 25.7%, considering a national prevalence of overweight equal to 34.6%. Conclusion: The incidence of hypertension in our study is similar to that reported two decades ago in cohorts from developed countries, which is consisting with the ongoing epidemiological transition in Latin America. We also confirmed the role of overweight as a risk factor for hypertension, accounting for about 1 out 4 incident cases. This finding highlights the importance of addressing overweight in our population.

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