Association of a combined panel of tumor infiltrating lymphocytes, plasma cells, and macrophages with recurrence of localized clear cell (cc) renal cell carcinoma (RCC) undergoing surgery.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 502-502
Author(s):  
Pooja Ghatalia ◽  
Jennifer Gordetsky ◽  
Sejong Bae ◽  
Stacey M Watkins ◽  
Sunil Sudarshan ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Tumor Recurrence ◽  
Plasma Cells ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Macrophage Infiltration ◽  
Composite Panel ◽  
Prognostic Impact ◽  
Urologic Oncology ◽  
Risk Of Recurrence

502 Background: Tumor infiltrating Programmed-Death (PD)-1 and FoxP3-expressing lymphocytes and macrophages appear to be associated with higher risk of recurrence in patients (pts) with ccRCC undergoing surgery for localized disease. We aimed to combine the presence of morphologically identified lymphocytes, plasma cells and macrophages into a readily available composite immune cell panel and to evaluate its association with tumor recurrence. Methods: We identified pts with ccRCC who underwent nephrectomy at UAB for whom we had annotation for objective tumor recurrence and a minimum follow-up of 2 years. Central pathology review was conducted by a single urologic oncology certified pathologist to capture pathologic variables (stage, grade, necrosis, histologic components, cystic changes) and immune cell (lymphocyte/plasma cell/macrophage) infiltration. Logistic regression (univariate and multivariate) analyses were conducted to evaluate the association of these variables with tumor recurrence. Results: Of the 159 identified and evaluable pts, 33 (20.7%) recurred and 126 did not. On univariate analyses, sarcomatoid/rhabdoid histologic components, lymphocyte/plasma cell infiltration, necrosis, pathological T stage and histologic grade were all statistically significantly associated with a risk of recurrence (p < 0.05). On multivariate analysis, in addition to pathologic stage (p = 0.0018), only the combination of higher lymphocyte/plasma cell and macrophage infiltration (p = 0.0347) was independently associated with recurrence; patients were 8.7 times more likely to recur (95% CI: 1.66, 45.28). Conclusions: A readily available and widely applicable composite panel of morphologically identified lymphocytes, plasma cells and macrophages infiltrating the tumor predicts recurrence of pts with localized ccRCC undergoing surgery, after controlling for clinical and pathologic prognostic factors. Our hypothesis-generating data require validation and further interrogation of specific markers expressed on immune cells may refine an immune panel that confers prognostic impact.

Immunoglobulin-Like Transcript 2 (ILT2) Is Not Differentially Expressed in MGUS and Myeloma, but Appears To Be Downregulated at an Earlier Stage of Plasma Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5039-5039
Author(s):  
Martin Schreder ◽  
Wolfgang Huebl ◽  
Gudrun Koch ◽  
Kathrin Strasser-Weippl ◽  
Niklas Zojer ◽  
...  
Keyword(s):  
Differential Expression ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Killer Cell ◽  
Differentially Expressed ◽  
Expression Level ◽  
Prognostic Impact ◽  
Clinical Parameters ◽  
Mrna Levels ◽  
Normal Plasma

Abstract Background: Immunoglobulin-like transcript 2 (ILT2/CD85j) belongs to the Ig superfamily and has homology to the killer cell inhibitory receptors (KIRs). It is expressed on natural killer (NK) cells, monocytes, macrophages, dendritic cells and (naive) B lymphocytes. A differential expression of ILT2 was described for monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Gene expression profiling studies found ILT2 to be downregulated 8.26 fold in myeloma as compared to MGUS, being the most differentially expressed gene between these two subsets. However, as RNA from CD138+ cells was used in this analysis, a varying percentage of normal, non-malignant plasma cells will impact on the results, especially in MGUS cases. Aims: We aimed to delineate ILT2 expression in different plasma cell subsets (normal compared to monoclonal cells) in MGUS and MM and the eventual prognostic impact of a differential expression level. Methods: ILT2 expression was measured by flow cytometry using a PE-conjugated antibody (clone HP-F1, Beckman Coulter) in a series of 30 MGUS patients and 91 myeloma patients. Phenotypically normal and malignant plasma cells were defined by differential expression of CD38, CD45, CD19 and CD56. Expression levels are given as mean fluorescence intensity (MFI) after correction for background staining. Results: ILT2 was not differentially expressed in monoclonal plasma cells from patients with MGUS (MFI median 112.0, range 13.5–274.4) and myeloma (MFI median 96.6, range 0.4–454.5). In contrast, monoclonal cells from MGUS and MM showed a significantly lower expression of ILT2 as compared to phenotypically normal plasma cells in the majority of samples (p=0.007). Results were confirmed by quantitative real time PCR studies in 25 MM patients showing a linear correlation of ILT2 mRNA levels with the intensity of ILT2 protein expression. ILT2 levels did not vary with state of disease and showed no correlation with clinical parameters or prognosis in our series of myeloma patients. Conclusions: In the majority of patients with monoclonal plasma cell disorders, ILT2 seems to be downregulated at an early stage of disease, i.e. upon transformation from a normal plasma cell to the MGUS/MM stage. The expression level of ILT2 in monoclonal plasma cells is neither correlated with the state of disease (MGUS versus newly diagnosed myeloma versus advanced disease) nor to prognosis of myeloma patients or other clinical parameters.

scholarly journals Tumor Immune Microenvironment Clusters in Localized Prostate Adenocarcinoma: Prognostic Impact of Macrophage Enriched/Plasma Cell Non-enriched Subtypes

2020 ◽  
Author(s):  
Neil K. Jairath ◽  
Mark W. Farha ◽  
Sudharsan Srinivasan ◽  
Ruple Jairath ◽  
Michael D. Green ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
M2 Macrophage ◽  
Significant Heterogeneity ◽  
Prognostic Impact ◽  
Cell Type ◽  
Immune Microenvironment ◽  
Immune Cell Type

Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas (n=496) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Analyses of progression-free survival (PFS), distant metastases, and overall survival (OS) were performed using Kaplan-Meier estimates and Cox-regression multivariable analyses. Results: Four immune clusters were identified, largely defined by plasma cell, CD4+ Memory Resting T Cells (CD4 MR), M0 and M2 macrophage content (CD4 MRHighPlasma CellHighM0LowM2Low, CD4 MRLowPlasma CellHighM0LowM2Low, CD4 MRHighPlasma CellLowM0HighM2Low, and CD4 MRHighPlasma CellLowM0LowM2High). The two macrophage-enriched/plasma cell non-enriched clusters (3&amp;4) demonstrated worse PFS (HR 2.24, 95% CI 1.46&ndash;3.45, p=0.0002) than the clusters 1&amp;2. No metastatic events occurred in the non-macrophage-enriched clusters. Comparing clusters 3 vs 4, in patients treated by surgery alone, cluster 3 had zero progression events (p&lt;0.0001). However, cluster 3 patients had worse outcomes after post-operative radiotherapy (p=0.018). Conclusion: Distinct tumor immune clusters with a macrophage-enriched phenotype and reduced plasma cell enrichment independently characterize an aggressive phenotype in localized prostate cancer that may differentially respond to treatment.

Prognostic impact of bone marrow CD138 immunohistochemistry (IHC) prior to autologous stem cell transplant (ASCT) for multiple myeloma (MM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8600-8600
Author(s):  
M. C. Foster ◽  
R. Christensen ◽  
J. Egan ◽  
J. Whitley ◽  
W. K. Chiu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Pearson Correlation ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Chi Squared

8600 Background: Low bone marrow plasma cell (BMPC) burden prior to ASCT for MM is associated with favorable outcomes, but is usually determined by morphologic evaluation of marrow aspirates, a method subject to variability in sampling and interpretation. It is unknown if CD138 IHC, a more sensitive measure of BMPC, predicts progression-free survival (PFS), overall survival (OS) or post-ASCT response. Methods: Consecutive patients (n=93) who underwent single ASCT for MM from 2001 to 2008 and had available, stainable bone marrow core biopsies (BMB) obtained <90 days prior to ASCT were included in this single-center retrospective cohort study. BMB and/or clot CD138 IHC staining were reviewed by blinded hematopathologists. Post-ASCT response, PFS, and OS were determined using the International Myeloma Working Group uniform response criteria. Results: Patients were highly cytoreduced prior to ASCT, with 50.5% of pts having 0–5%, 21.5% having 6–10%, 20.4% having 11–20%, and 7.5% having >20% BMPC by CD138 analysis. BMPC% by CD138 IHC correlated with aspirate BMPC% [Pearson correlation coefficient=0.48, 95%CI (0.30, 0.63)]. In 12.6% of patients, BMPC% by CD138 IHC was ≥10% more than the aspirate count. Patients with ≤5% BMPC were more likely to achieve or maintain a CR or VGPR at initial post-ASCT restaging than those with >5% BMPC: Odds Ratio (95% CI) 6.91 (2.12, 22.57), p=. 0005 (chi-squared). With median follow up of 15.4 months for the ≤5% BMPC group and 19.3 months for the >5% BMPC group, 34/93 patients have progressed or died, with no difference between groups. By Kaplan-Meier analysis, PFS was similar regardless of BMPC [3 year estimated PFS (95%CI): ≤5%BMPC, 49.9% (29.4, 70.4) vs. >5%BMPC, 45.5% (26.7, 64.3); HR=1.24 (0.62, 2.49), p=.55, log-rank]. There was no difference in OS [3 year estimated OS (95%CI): ≤5%BMPC, 71.0% (49.7, 92.3) vs. >5%BMPC, 81.8% (66.2, 97.4); HR=0.61 (0.21, 1.78), p=.36, log-rank]. Conclusions: Detection of ≤5% BMPC by CD138 IHC prior to ASCT predicts attainment or maintenance of post-transplant CR/VGPR and correlates with plasma cell morphology. Differences in PFS or OS may emerge with additional follow-up, or if more patients with a higher content of residual plasma cells were transplanted. [Table: see text]

Prognostic impact of tumor-associated B-cells and plasma cells in esophageal and gastric adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 63-63
Author(s):  
Richard Fristedt ◽  
Charlotta Hedner ◽  
David Borg ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
...  
Keyword(s):  
Immune System ◽  
B Cell ◽  
Gastric Adenocarcinoma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
High Density ◽  
Prolonged Survival ◽  
Cell Infiltration ◽  
Additional Patient ◽  
Prognostic Impact

63 Background: Tumor immune cell infiltration has been shown to influence the prognosis and treatment prediction in several types of cancer and the focus has largely been on the innate immune system as well as the cell-mediated immune response. There are, however, recent findings suggesting an important role for the humoral immune system in stemming cancer progression. The aim of this study was therefore to investigate the prognostic impact of B cell and plasma cell infiltration in esophageal and gastric cancer. Methods: Immunohistochemical expression of the pan B-cell marker CD20 and plasma cell markers CD138 and immunoglobulin kappa C (IGKC), were analyzed in tissue microarrays (TMA) from primary tumors in a cohort of 174 consecutive, surgically treated cases of gastro-esophageal adenocarcinoma. A multiplier of intensity and fraction was calculated, and the median value was used for prognostic cut-off. Kaplan-Meier analysis, univariable and multivariable Cox regression analysis, adjusted for age, TNM-stage, resection margins and adjuvant chemotherapy, were used to determine the impact of IGKC, CD20 and CD138 expression on overall survival (OS). Results: A high density of IGKC+ plasma cells was significantly associated with a prolonged survival in esophageal (HR 0.41, 95% CI 0.21-0.78) and gastric adenocarcinoma (HR 0.50, 95% CI 0.28-0.88). A high density of CD138+ plasma cells was also significantly associated with prolonged survival but only in gastric adenocarcinoma (univariable HR 0.48, 95% CI 0.27-0.86, multivariable HR 0.51; 95% CI 0.27-0.97)). IGKC+ plasma cell expression remained significant in multivariable analysis, for esophageal (HR 0.50, 95% CI 0.26-0.97) and gastric adenocarcinoma (HR 0.50, 95% CI 0.27-0.94). There was no significant association between the density of CD20+ cells and survival. Conclusions: Our findings show, for the first time, that a higher density of stromal plasma cells correlates with a prolonged survival in both esophageal and gastric adenocarcinoma. These are new and encouraging findings that warrant further evaluation in additional patient cohorts.

scholarly journals Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 39 ◽  
Author(s):  
Rainer C. Miksch ◽  
Markus B. Schoenberg ◽  
Maximilian Weniger ◽  
Florian Bösch ◽  
Steffen Ormanns ◽  
...  
Keyword(s):  
Hot Spots ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Free Survival ◽  
Staging Systems ◽  
Infiltrating Lymphocytes ◽  
The Impact

In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3+, CD8+, and CD20+ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3+ TILs predicted progression after 12 months. The location of TILs’ hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

scholarly journals Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Carlos Fernández de Larrea ◽  
Robert Kyle ◽  
Laura Rosiñol ◽  
Bruno Paiva ◽  
Monika Engelhardt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Prognostic Impact ◽  
Cell Leukemia ◽  
Consensus Definition ◽  
Cell Percentage ◽  
Primary Plasma Cell Leukemia

AbstractPrimary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.

scholarly journals Tumor Immune Microenvironment Clusters in Localized Prostate Adenocarcinoma: Prognostic Impact of Macrophage Enriched/Plasma Cell Non-Enriched Subtypes

2020 ◽  
Vol 9 (6) ◽  
pp. 1973
Author(s):  
Neil K. Jairath ◽  
Mark W. Farha ◽  
Sudharsan Srinivasan ◽  
Ruple Jairath ◽  
Michael D. Green ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
M2 Macrophage ◽  
Significant Heterogeneity ◽  
Prognostic Impact ◽  
Cell Type ◽  
Immune Microenvironment ◽  
Immune Cell Type

Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas (n = 492) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Analyses of progression-free survival (PFS), distant metastases, and overall survival (OS) were performed using Kaplan–Meier estimates and Cox regression multivariable analyses. Results: Four immune clusters were identified, largely defined by plasma cell, CD4+ Memory Resting T Cells (CD4 MR), and M0 and M2 macrophage content (CD4 MRHighPlasma CellHighM0LowM2Mid, CD4 MRLowPlasma CellHighM0LowM2Low, CD4 MRHighPlasma CellLowM0HighM2Low, and CD4 MRHighPlasma CellLowM0LowM2High). The two macrophage-enriched/plasma cell non-enriched clusters (3 and 4) demonstrated worse PFS (HR 2.24, 95% CI 1.46–3.45, p = 0.0002) than the clusters 1 and 2. No metastatic events occurred in the plasma cell enriched, non-macrophage-enriched clusters. Comparing clusters 3 vs. 4, in patients treated by surgery alone, cluster 3 had zero progression events (p < 0.0001). However, cluster 3 patients had worse outcomes after post-operative radiotherapy (p = 0.018). Conclusion: Distinct tumor immune clusters with a macrophage-enriched, plasma cell non-enriched phenotype and reduced plasma cell enrichment independently characterize an aggressive phenotype in localized prostate cancer that may differentially respond to treatment.

scholarly journals Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition

Haematologica ◽  
2017 ◽  
Vol 102 (6) ◽  
pp. 1099-1104 ◽  
Author(s):  
Miquel Granell ◽  
Xavier Calvo ◽  
Antoni Garcia-Guiñón ◽  
Lourdes Escoda ◽  
Eugènia Abella ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Prognostic Impact ◽  
Cell Leukemia

scholarly journals Prognostic significance of S100A8-positive immune cells in relation to other immune cell infiltration in pre-invasive and invasive breast cancers

2020 ◽  
Author(s):  
Ji Won Woo ◽  
Yul Ri Chung ◽  
Milim Kim ◽  
Hye Yeon Choi ◽  
Soomin Ahn ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Invasive Carcinoma ◽  
Immune Cell ◽  
Dynamic Change ◽  
Prognostic Significance ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Breast Cancers

Abstract Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression through both immunologic and non-immunologic mechanisms. This study was conducted to evaluate the expression of S100A8, a well-known MDSC marker, and the significance of its expression in pre-invasive and invasive breast cancers. S100A8 expression in tumor cells (TCs) and immune cells (ICs) was assessed by immunohistochemistry, and its association with clinicopathologic features and infiltration of other IC subsets including CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocytes (TILs) and PD-L1+ ICs was evaluated. S100A8 expression in TCs and ICs showed a positive correlation in pre-invasive carcinoma and invasive carcinoma. S100A8+ ICs, but not S100A8+ TCs, were significantly higher in number in invasive carcinoma than in pre-invasive carcinoma. Infiltration of S100A8+ ICs was revealed as a poor prognostic indicator in pre-invasive and invasive carcinomas, especially in hormone receptor-positive subgroup. Infiltration of CD4+, CD8+, and FOXP3+ TIL subsets and PD-L1+ ICs was significantly higher in S100A8+ IC (+) group than in S100A8+ IC (−) group. Combined analyses of IC subset infiltration revealed that infiltration of S100A8+ ICs was associated with poor clinical outcome in the PD-L1+ IC (−), CD8+ TIL-low, and FOXP3+ TIL-low subgroups. In conclusion, S100A8+ ICs seem to undergo a dynamic change during breast cancer progression in association with other IC subset infiltration. The prognostic impact of S100A8+ IC infiltration was greater in less immunogenic tumors.

Sign in / Sign up

Export Citation Format

Share Document