scholarly journals THE MAIN PARAMETERS OF CELLULAR IMMUNITY IN PATIENTS WITH TRIPLE-NEGATIVE BREAST CANCER: RELATIONSHIP WITH EFFICIENCY OF CHEMOTHERAPY

2018 ◽  
Vol 20 (5) ◽  
pp. 667-680 ◽  
Author(s):  
A. I. Chertkova ◽  
E. G. Slavina ◽  
E. K. Shoua ◽  
L. G. Zhukova ◽  
M. A. Okruzhnova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Overall Survival ◽  
T Cells ◽  
Disease Progression ◽  
Triple Negative ◽  
Lymphocyte Subsets ◽  
Nkt Cells ◽  
Peripheral Blood Lymphocytes ◽  
Initial State

Chemotherapy is among the primary methods of treating advanced breast cancer. It was shown that clinical efficacy of various chemotherapeutic agents in many cases depends not only on their direct cytostatic and/or cytotoxic effect upon tumor cells, but also on their ability to modulate phenotype of the tumor cells and to influence anti-tumor immune response. Initial state of the immune system and its response to treatment is crucial. Antitumor response involves cells of innate and adaptive immunity (NK, NKT, T cells). These populations are heterogeneous and contain, e.g., cells with antitumor activity and regulatory (suppressor) cells that suppress immune response and promote tumor progression. The aim of this work was to determine the relationship between the initial state of cellular immunity of patients suffering from locally advanced breast cancer with triple negative phenotype, and clinical effect of chemotherapy (cisplatin + doxorubicin/paclitaxel), and studying effects of the therapy upon subpopulation profiles of peripheral blood lymphocytes in the patients. We registered the terms of the disease progression as well as overall survival and progression-free survival. The disease progressed in 25 of 53 cases (47.2%) whereas 28 of 53 patients (52.8%) remained progression-free. The observation period was 35.5 months. Laboratory examination of the patients included immunophenotyping of peripheral blood lymphocytes and determination of NK cell cytotoxic activity before and after chemotherapy. Percentages of effectors and regulatory lymphocyte populations were determined. The results obtained showed that, for some lymphocyte subsets, the pre-treatment differences of cell percentage deviations from control were found between the progression-free groups and patients with progression of the disease. The differences in percentages of NKT cells and lymphocytes expressing CD25 activation marker proved to be most significant. Decreased number of NKT cells and activated CD25+ lymphocytes prior to chemotherapy was associated with increased probability of disease progression. Reduced percentage of NKT cells against control was observed in 56% of patients from the progression group (PD), and only 21.4% in the group free of disease progression (DF). [OR = 4.6 (95% CI 1.4 to 15.4)]. Percentage of CD25+ lymphocytes was decreased from 68.2% in the PD group, and 28.6% for DF patients [OR = 5.4 (95% CI 1.6-18.1)]. We studied relationships between the overall survival (OS) and percentage of perforin-containing NK, NKT, and T cells, and mean perforin fluorescence density (PFD) in these lymphocyte subsets in 26 of the 53 patients before treatment. A statistically significant positive correlation was revealed between OS and perforin PFD in all the three cell populations under study. Normalization of the parameters altered before treatment, and an increase of T cell numbers was observed in the disease-free patients.

scholarly journals Nomogram Personalizes and Visualizes the Overall Survival of Patients with Triple-Negative Breast Cancer Based on the Immune Genome

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Peipei Wang ◽  
Yang Fu ◽  
Yueyun Chen ◽  
Qing Li ◽  
Ye Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Risk Score ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Novel Therapy ◽  
Immune Biomarkers ◽  
Poorly Differentiated ◽  
Immune Related Genes

Background. Triple-negative breast cancer (TNBC) is usually poorly differentiated, highly invasive, susceptible to distant metastasis, and less responsive to endocrine and targeted therapy. However, immunotherapy is a promising treatment for TNBC patients recently. Methods. The prognostic value of immune-related genes (IRGs) was explored by using RNA sequencing and microarray data of 123 and 107 TNBC patients from TCGA and GEO databases, respectively. Results. In TCGA database, GO and KEGG pathway analysis of 119 differential IRGs indicated that they actively participate in the interaction of cytokines and receptors. A nomogram model constructed by the prognosis-related CCL25, IL29, TDGF3, GPR44, and GREM2 in the IRGs could personalize and visualize the 1-, 2-, 3-, 4-, and 5-year overall survival (OS) of TNBC patients. Moreover, TNBC patients could be defined as low-risk ( risk   score < 194 ) or high-risk ( risk   score ≥ 194 ) cohorts based on the risk score derived from the nomogram model. The results could be validated by the GSE58812 dataset. Furthermore, the risk score was an independent risk factor for TNBC patients ( HR = 1.019 , 95% CI 1.012-1.027, p < 0.001 ) and was positively related to stage ( p = 0.017 ). Interestingly, the risk score could reflect the infiltration of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, and neutrophils. Conclusion. These findings provided a reference for personalized OS prediction in TNBC patients and might be potential immune biomarkers for designing novel therapy.

Prolonged Survival of Dendritic Cell–Vaccinated Melanoma Patients Correlates With Tumor-Specific Delayed Type IV Hypersensitivity Response and Reduction of Tumor Growth Factor β-Expressing T Cells

2009 ◽  
Vol 27 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Mercedes N. López ◽  
Cristian Pereda ◽  
Gabriela Segal ◽  
Leonel Muñoz ◽  
Raquel Aguilera ◽  
...  
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
T Cells ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Disease Progression ◽  
Stage Iv ◽  
Stage Iii ◽  
Type Iv ◽  
Melanoma Patients

PurposeThe aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines.Patients and MethodsForty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records.ResultsThe overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) β+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001).ConclusionOur findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFβ+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.

scholarly journals 870 Targeting GCN2 kinase-driven stress response inactivation to restore tumor immunity in metastatic triple negative breast cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A911-A911
Author(s):  
Hariprasad Vankayalapati ◽  
Kyle Medley ◽  
Zhaoliang Li ◽  
Dongqing Yan ◽  
David Bearss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acids ◽  
Overall Survival ◽  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Small Molecule ◽  
Triple Negative ◽  
Nutrient Stress ◽  
List Type

BackgroundPatients with PD-L1-positive metastatic triple-negative breast cancers (mTNBC) who have been treated with atezolizumab+nab-paclitaxel had a clinically meaningful overall survival extension of 9.5 months compared to nab-paclitaxel alone, although overall survival in overall population was not statistically significant. Unlike many other cancers, immunotherapy for breast cancer has had limited success, due to the fact that there are very few T cells in the tumor microenvironment of mTNBC patients. Identifying ways to boost immunotherapy responses could change the paradigm of mTNBC, a disease still difficult to treat. The highly proliferative nature of tumor cells, along with infiltration of myeloid cells into the tumors, leads to depletion of nutrients such as functional/natural amino acids. This metabolically stressful milieu causes activation of nutrient stress pathways, autophagy, and repressed immune responses. A key meditator of this nutrient stress pathway is a cytoplasmic Ser/Thr protein kinase called General Control Nonderepressible 2 (GCN2), also called EIF2AK4. GCN2 switches on following reduction of amino acids, and its activity results in T cell inactivation, T cell death, regulatory T cell expansion, and the potentiation of myeloid-derived suppressor cells (MDSCs).MethodsWe have developed and synthesized a series of novel small molecule immunotherapeutic agents that reversibly bind to GCN2 kinase, competitively block the ATP site, and elicit pharmacological responses in immune cells and in breast cancer cells.ResultsGCN2 cell-free kinase binding, kinome selectivity, pGCN2, pEIF2α, ATF-4 phosphorylation inhibition assays were performed. We confirmed on-target efficacy and tested the potency of our lead GCN2 inhibitor HCI-1046. HCI-1046 demonstrated potent activity, with an IC50 of 36 nM in inhibiting GCN2 kinase and exhibited cellular efficacy with an IC50 of 0.1 to 1.0 μM range. Our preliminary results support the hypothesis that the inhibition of GCN2 reinstates anti-tumor immunity and blocks tumor progression in breast cancer models. In vivo PK studies of HCI-1046 in rodents showed excellent PK properties; 55% oral bioavailability, low clearance, and >5 hour half-life.ConclusionsThus, HCI-1046 is nominated as a pre-clinical agent. Additional data regarding evaluation of the effects of HCI-1046 on the MDSC-suppressive function on T cells using ELISpot assays with breast cancer patient samples, and mouse model efficacy studies will be discussed.ReferencesEkiz HA, Lai SA, Gundlapalli H, Haroun F, Williams MA, Welm AL. Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth. Oncoimmunology 2018;7(9):e1480286.Toogood PL. Small molecule immuno-oncology therapeutic agents. Bioorg Med Chem Lett 2018;28(3):319–329.Ravindran R, Loebbermann J, Nakaya HI, Khan N, Ma H, Gama L, Machiah DK, Lawson B, Hakimpour P, Wang YC, Li S, Sharma P, Kaufman RJ, Martinez J, Pulendran B. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation. Nature 2016;531(7595):523–527.Brazeau JF, Rosse G. Triazolo[4,5-d]pyrimidine derivatives as inhibitors of GCN2. ACS Med Chem Lett 2014;5(4):282–3.

scholarly journals Interleukin-17-based cytokine signaling as a determinant for tumor immune microenvironment with prognostic value in triple-negative breast cancer

2021 ◽  
Author(s):  
Victor C. Kok ◽  
Charles C.N. Wang ◽  
Szu-Han Liao ◽  
De-Lun Chen
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Nk Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Receptor Interaction ◽  
Cytokine Signaling ◽  
Interleukin 17

Abstract Background: Only a proportion of triple-negative breast cancer (TNBC) is immunotherapy-responsive. We hypothesized that the tumor microenvironment (TME) might influence the outcomes of TNBC and investigated the relevant signaling pathways. Methods: RNA-seq data of 115 TNBC samples and 112 normal adjacent tissues were retrieved for ESTIMATE, CIBERSORTx, X2K, KEGG, and GSVA analyses. The immune score (IS) and stromal score (SS) were calculated and correlated with the overall survival (OS) in TNBC. Finally, we validated the altered transcription factor (TF) genes in the cBioPortal. Results: The SS is a good predictor of the OS (better survival in SS-low patients; P = 0.0081). In line with these results, when compared with IS-low/SS-high patients, IS-high/SS-low patients showed a better OS (P = 0.045). Moreover, macrophages were polarized toward the M2 phenotypes in IS-low/SS-high patients (P < 0.001). Compared with IS-low/SS-high patients, CIBERSORTx also showed that IS-high/SS-low patients had an increased number of memory B cells, CD8+ T cells (14.8% vs. 3.7%, p = 0.0286), activated CD4+ memory T cells, follicular helper T cells, and activated NK cells in the TME; additionally, fewer resting NK cells were detected in the TME (P = 0.0108). Additionally, there were 284 upregulated and 367 downregulated DEGs (Differentially Expressed Genes) in IS-high/SS-low, and 187 upregulated and 183 downregulated DEGs in IS-low/SS-high patients. KEGG analysis further revealed that the DEGs were enriched in the IL-17 and cytokine-cytokine receptor interaction pathways. Of note, as per the cBioPortal platform, we discovered that 13% of ER-negative, HER2-unamplified BC patients harbored IL17RA deep deletions and 25% harbored TRAF3IP2 amplifications; interestingly, the nine altered TF genes were associated with significantly worse relapse-free survival and OS, in the context of 2,377 and 4,819 BC patients, respectively.Conclusions: The TME with different immune cell components influences the survival of TNBC patients. IS-high/SS-low patients show a better overall survival. Further studies are required to examine whether an immune/stromal state also predicts the response to immunotherapy.

Dynamic relationship between cycling kinetics of triple-negative breast cancer and tumor infiltrating immune cells.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1100-1100
Author(s):  
Ishita Choudhary ◽  
Sergey Klimov ◽  
Padmashree C.G. Rida ◽  
Angela Ogden ◽  
Andrew R. Green ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
T Cells ◽  
Triple Negative Breast Cancer ◽  
Immune Cells ◽  
Triple Negative ◽  
Antitumor Immune Response ◽  
M2 Macrophage ◽  
Slow Cycling ◽  
Kinetics Of

1100 Background: Recent studies show strong correlation between tumor infiltrating lymphocytes (TILs) and triple-negative breast cancer (TNBC) patient survival. CD8+ T cells serve as a favorable prognostic marker for TNBC. In addition, other cells such as CD4+ T cells, macrophages, B cells, and Tregs also infiltrate tumors. In this study, we delineate a strong relationship between the cycling kinetics of proliferating cells in TNBCs and antitumor immune response. Methods: A multi-institutional study performed by our group has previously shown that KAMS (Ki67-Adjusted Mitotic Score) provides a measure of the cycling kinetics of proliferating tumor cells and robustly stratifies TNBC patients into slow cycling (low KAMS) cyclophosphamide-methotrexate-fluorouracil (CMF)-responsive and fast cycling (high KAMS) CMF-resistant subgroups. In this study, we reviewed clinical data from 124 CMF-treated TNBC patients from Nottingham Hospital and sought correlations between cycling kinetics (High/Low KAMS) and tumor infiltrating immune cells. Results: We found that slow cycling TNBCs had higher mean expression of tumor infiltrating immune cells than fast cycling TNBCs. Intratumoral CD68 (p = 0.003), CD3 (p = 0.006), CD20 (p = 0.01), FOXP3 (p = 0.01), and total numbers of intratumoral and stromal CD68 (p = 0.01) and CD3 (p = 0.03) expressing cells were found to be significantly higher in low KAMS tumors than in high KAMS tumors. Of these biomarkers, CD68 was significantly associated with patients’ breast cancer-specific survival (BCSS): (a) low KAMS, high CD68 TNBCs had better BCSS than low KAMS, low CD68 (p = 0.01) TNBCs, and (b) high KAMS, low CD68 cases had better BCSS than high KAMS, high CD68 cases. Conclusions: Our observation that there are more TILs in slow cycling TNBCs suggests that there may be a dynamic cross-regulation between cycling kinetics and antitumor immune response. From our surprising observation that CD68 exerts polar roles in low/high KAMS subgroups, we propose that distinctions in M1 and M2 macrophage subsets in slow and fast cycling TNBCs may correlate with distinct outcomes. In addition, metabolic competition between tumor and immune cells may determine the level and function of TILs.

scholarly journals ASSOCIATION OF NKT- AND ACTIVATED CD25+ PERIPHERAL BLOOD LYMPHOCYTES WITH DISEASE FREE AND OVERALL SURVIVAL OF TRIPLE NEGATIVE BREAST CANCER PATIENTS

2020 ◽  
Vol 19 (6) ◽  
pp. 66-72
Author(s):  
A. I. Chertkova ◽  
E. G. Slavina ◽  
T. N. Zabotina ◽  
Z. G. Kadagidze ◽  
E. K. Shoua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Peripheral Blood ◽  
Triple Negative ◽  
Peripheral Blood Lymphocytes ◽  
Initial Number ◽  
Blood Lymphocytes ◽  
The Relationship

Background. We previously found that a decrease in the number of NKT cells and activated CD 25+ peripheral blood lymphocytes (PBLs) before neoadjuvant chemotherapy was associated with an increased likelihood of disease progression in patients with locally advanced triple-negative breast cancer (TN BC).The purpose of this study was to determine the relationship between the initial number of NKT-and CD 25+ PBLs and relapsefree survival (RFS)/overall survival (OS ) in patients with TN BC who received neoadjuvant chemotherapy with cisplatin and paclitaxel followed by surgery.Material and Methods. The study included patients with stage II and III TN BC. The follow-up time was 36 and 66.9 months. Immediately before chemotherapy, the percentage of CD 3+CD 16+CD 56+ (NKT) -, CD 25+- and CD 8+ PBLs was determined by flow cytometry. Statistical analysis of the data was carried out using the Statistics 7 software package. The Kaplan-Meier method was used to determine the relationship between immunological parameters and RFS/ OS .Results. The decreased level of NKT cells before treatment was associated with a decrease in the 3-year RFS [Me: 20.1 (0.533 and 39.7) months] compared to that observed in patients with higher percentage of these cells than in the control (Me was not achieved). There were no statistically significant differences in the 3-year OS between the groups. The initially reduced number of CD 25+ lymphocytes in comparison with the control was associated with decreased rates of both RFS and OS . The difference in DFS and OS was more significant between the groups of patients who simultaneously had an increased initial number of both NKT and CD 25+ cells and patients in whom both cell populations were below normal levels.Conclusion. The initial (prior to chemotherapy) number of NKT and activated CD 25+ PBLs can apparently be a predictive factor in TN BC patients, who received neoadjuvant chemotherapy with cisplatin and paclitaxel. 

scholarly journals Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Francesco Schettini ◽  
Nuria Chic ◽  
Fara Brasó-Maristany ◽  
Laia Paré ◽  
Tomás Pascual ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
High Activity ◽  
Triple Negative ◽  
Her2 Expression ◽  
Drug Conjugates ◽  
Molecular Features ◽  
Biological Heterogeneity ◽  
Antibody Drug

AbstractNovel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

Applicability of PD-L1 tests to tailor triple-negative breast cancer treatment in Brazil

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Kátia Ramos Moreira Leite ◽  
Carlos Henrique Barrios ◽  
Antônio Carlos Buzaid ◽  
Débora Gagliato ◽  
Helenice Gobbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Median Overall Survival ◽  
Triple Negative ◽  
Breast Cancer Treatment ◽  
Main Text ◽  
Critical Questions ◽  
Online Panel ◽  
Active Interest

Abstract Background Triple-negative breast cancer (TNBC) is a heterogeneous disease that represents 10–20% of breast cancer cases. The prognosis for advanced TNBC is usually poor, with a median overall survival of approximately 18 months or less. Main text New targeted therapies such as anti-PD-L1 agents are emerging as an option to treat advanced TNBC. A panel of 6 national experts with an active interest in breast cancer convened online. Panel members had either clinical or pathology experience in breast cancer. The experts pre-defined critical questions in the management of PD-L1 in TNBC, and a literature review was performed for selected topics before the online meeting. Conclusion The experts led active discussions involving a multidisciplinary team comprising pathologists and clinical oncologists. The meeting served to discuss the most relevant issues. A total of 10 critical questions for PD-L1+ TNBC were debated and are presented in this review. This article discusses the current landscape for PD-L1 tests in TNBC in Brazil.

scholarly journals Claudin-Low Breast Cancer Inflammatory Signatures Support Polarization of M1-Like Macrophages with Protumoral Activity

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2248
Author(s):  
Mayra Cecilia Suárez-Arriaga ◽  
Alfonso Méndez-Tenorio ◽  
Vadim Pérez-Koldenkova ◽  
Ezequiel M. Fuentes-Pananá
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative ◽  
Tumor Subtype ◽  
Blood Monocytes ◽  
Adverse Clinical Outcome ◽  
M1 Macrophages ◽  
Peripheral Blood Monocytes ◽  
Gm Csf ◽  
Th1 Immune Response

We previously reported that triple-negative breast cancer (BRCA) cells overexpress the cytokines GM-CSF, G-CSF, MCP-1, and RANTES, and when monocytes were 3-D co-cultured with them, M1-like macrophages were generated with the ability to induce aggressive features in luminal BRCA cell lines. These include upregulation of mesenchymal and stemness markers and invasion. In this study, we stimulated peripheral blood monocytes with the four cytokines and confirmed their capacity to generate protumoral M1-like macrophages. Using the METABRIC BRCA database, we observed that GM-CSF, MCP-1, and RANTES are associated with triple-negative BRCA and reduced overall survival, particularly in patients under 55 years of age. We propose an extended M1-like macrophage proinflammatory signature connected with these three cytokines. We found that the extended M1-like macrophage signature coexists with monocyte/macrophage, Th1 immune response, and immunosuppressive signatures, and all are enriched in claudin-low BRCA samples, and correlate with reduced patient overall survival. Furthermore, we observed that all these signatures are also present in mesenchymal carcinomas of the colon (COAD) and bladder (BLCA). The claudin-low tumor subtype has an adverse clinical outcome and remains poorly understood. This study places M1 macrophages as potential protumoral drivers in already established cancers, and as potential contributors to claudin-low aggressiveness and poor prognosis.

scholarly journals Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

2021 ◽  
Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

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