scholarly journals RARE-34. TUMOR IMMUNITY AND EXTRACRANIAL METASTASES, AND MECHANISM OF PD-L1 EXPRESSION IN INTRACRANIAL SOLITARY FIBROUS TUMOR/HEMANGIOPERICYTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi228-vi229
Author(s):  
Dai Kamamoto ◽  
Kentaro Ohara ◽  
Yohei Kitamura ◽  
Kazunari Yoshida ◽  
Hikaru Sasaki
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Immunity ◽  
Solitary Fibrous Tumor ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
C Terminus ◽  
Fibrous Tumor ◽  
Extracranial Metastases

Abstract Intracranial solitary fibrous tumor (SFT) /hemangiopericytoma (HPC) are rare, however, these tumors are often associated with aggressive clinical course with recurrence and/or extracranial metastasis. PD-1, PD-L1 play important roles as immune-checkpoint mediators within tumor microenvironment, and the antibodies to these molecules are now approved for the treatment of various kinds of cancers. Some mechanisms of activation of PD-L1 are reported, including cytokines or chemokines from immune cells in tumor microenvironment, and genetic mutations such as translocation, or amplification. We have investigated the expression of PD-1, PD-L1, and tumor infiltrating lymphocytes (TIL) in 16 cases of SFT/HPC by immunohistochemistry. Kaplan-Meier method and log-rank/Wilcoxon tests were used to analyze the relationship between their expression with overall survival (OS), progression free survival (PFS), metastasis free survival (MFS), and time to treatment failure (TTF; metastasis or death). Additionally, we have analyzed amplification of PD-L1 gene by FISH, translocation between promotor region of CIITA and PD-L1 by PCR, and mutation in 3’-UTR by immunohistochemistry with antibody recognizes C-terminus (clone; SP-142) of PD-L1. PD-L1 was expressed in most of tumor cells. The intensity of PD-L1 expression was negatively associated with MFS (p=0.04), and diffuse pattern of PD-L1 expression showed trends towards shorter TTF compared with partial expression (p=0.08). Notably, with the combination analysis of PD-L1 and CD8(+) TIL, the diffuse PD-L1 expression with less CD8(+) was significantly associated with shorter TTF (p=0.005). However, there was no significant relevance between the expression of those immune-checkpoint molecules and OS or PFS. Although neither amplification of PD-L1 gene, 9p24.1, nor translocation between CITTA and PD-L1 were observed, difference in immunohistochemistry with two different anti-bodies was observed. In intracranial SFTs/HPCs, tumor immunity mechanism associated with PD-1/PD-L1 may play an important role in their extracranial metastases, and mutation in 3’-UTR may be a cause of PD-L1 activation in SFT/HPC.

scholarly journals Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis

Sarcoma ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
P. Schöffski ◽  
I. Timmermans ◽  
D. Hompes ◽  
M. Stas ◽  
F. Sinnaeve ◽  
...  
Keyword(s):  
Solitary Fibrous Tumor ◽  
Systemic Therapy ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Response Rates ◽  
Free Survival ◽  
Metachronous Metastasis ◽  
Third Line ◽  
Fibrous Tumor

Background. Solitary fibrous tumor (SFT) is a rare variant of soft tissue sarcoma (STS). Materials and Methods. We reviewed SFT patients (pts) treated at our institution between 12/1990 and 09/2017. Results. We identified 94 pts with a median follow-up (mFU) of 4.7 years (range: 0.1–21.53). Primary sites were the chest (33%), abdomen (21.3%), brain (12.8%), and extremities (9.6%); 6.4% of pts presented with synchronous metastasis. Median overall survival (mOS) from the first diagnosis was 56.0 months (m) (0.3–258.3). Doege–Potter syndrome was seen in 2.1% of pts. Primary resection was performed in 86 pts (91.5%). Median progression-free survival was 34.1 m (1.0–157.1), and 43% of pts stayed SFT-free during FU. Local recurrence occurred in 26.7% after a mFU of 35.5 m (1.0–153.8), associated with an OS of 45.1 m (4.7–118.2). Metachronous metastasis occurred in 30.2% after a mFU of 36.0 m (0.1–157.1). OS in metastatic pts was 19.0 m (0.3–149.0). Systemic therapy was given to 26 pts (27.7%) with inoperable/metastatic disease. The most common (57.7%) upfront therapy was doxorubicin, achieving responses in 13.3% of pts with a PFS of 4.8 m (0.4–23.8). In second line, pts were treated with ifosfamide or pazopanib, the latter achieving the highest response rates. Third-line treatment was heterogeneous. Conclusion. SFT is an orphan malignancy with a highly variable clinical course and a considerable risk of local failure and metachronous metastasis. Surgery is the only curative option; palliative systemic therapy is used in inoperable/metastatic cases but achieves low response rates. The highest response rates are seen with pazopanib in second/third line.

scholarly journals Characterization of immunoreactivity with whole-slide imaging and digital analysis in high-grade serous ovarian cancer

Tumor Biology ◽  
2020 ◽  
Vol 42 (11) ◽  
pp. 101042832097140
Author(s):  
Tiina Jäntti ◽  
Satu Luhtala ◽  
Johanna Mäenpää ◽  
Synnöve Staff
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cell ◽  
Granzyme B ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Serous Carcinoma ◽  
High Grade ◽  
Whole Slide Imaging ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Ovarian cancer is the most lethal of gynecological cancers with 5-year survival rate of ca. 45%. The most common histologic subtype is high-grade serous carcinoma, which typically is presented with advanced stage and development of chemoresistance. Therefore, new treatment options, including immunotherapies, are needed. Understanding the features of the immune cell populations in the tumor microenvironment is essential for developing personalized treatments and finding predictive biomarkers. Digital image analysis may enhance the accuracy and reliability of immune cell infiltration assessment in the tumor microenvironment. The aim of this study was to characterize tumor microenvironment in a retrospective cohort of high-grade serous carcinoma samples with whole-slide imaging and digital image analysis. Formalin-fixed paraffin-embedded high-grade serous carcinoma tumor tissue samples (n = 67) were analyzed for six immunohistochemical stainings: CD4, CD8, FoxP3, granzyme B, CD68, and CD163. The stained sample slides were scanned into a digital format and assessed using QuPath 0.1.2 and ImageJ software. Staining patterns were associated with clinicopathological data. The higher numbers of intraepithelial CD8+, CD163+, and granzyme B+ immune cells were associated with survival benefit when analyzed individually, while high levels of both CD8+ and granzyme B+ tumor-infiltrating lymphocytes were an independent prognostic factor in the Cox multivariate regression analysis (median progression-free survival; hazard ratio = 0.287, p = 0.002). Specimens taken after administration of neoadjuvant chemotherapy presented with lower FoxP3+ tumor-infiltrating lymphocyte density (Fisher’s exact test, p = 0.013). However, none of the studied immunomarkers was associated with overall survival or clinical factors. Tumors having high amount of both intraepithelial CD8+ and granzyme B+ tumor-infiltrating lymphocytes showed better progression-free survival, possibly reflecting an activated immune state in the tumor microenvironment. The combined positivity of CD8 and granzyme B warrants further investigation with respect to predicting response to immune therapy. Neoadjuvant chemotherapy may have an effect on the tumor microenvironment and therefore on the response to immuno-oncologic or chemotherapy treatments.

scholarly journals Malignant Solitary Fibrous Tumor of the Kidney: Report of the First Case Managed with Interferon

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Javier Cuello ◽  
Ricardo Brugés
Keyword(s):  
Solitary Fibrous Tumor ◽  
Distant Metastasis ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Prospective Evaluation ◽  
Free Survival ◽  
Solitary Fibrous Tumors ◽  
First Case ◽  
Fibrous Tumor

Solitary fibrous tumors of the kidney are extremely rare tumors with unpredictable behavior. We describe a case of a patient with a solitary fibrous tumor of kidney with malignant findings with distant metastasis and nephrectomy managed with subcutaneous interferon achieving 23 months of progression-free survival. To date there is no prospective evaluation of any specific modality of treatment, but the surgical management and long-term followup are the only ones so far recommended strategies in the management of these patients. Studies are awaited with more patients to evaluate the different strategies of systemic therapy reported so far to allow adding survival benefit.

scholarly journals Emerging Trends for Radio-Immunotherapy in Rectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1374
Author(s):  
Claudia Corrò ◽  
Valérie Dutoit ◽  
Thibaud Koessler
Keyword(s):  
Rectal Cancer ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
T Cell Infiltration ◽  
Emerging Trends ◽  
Tumor Mutational Burden ◽  
Microsatellite Stability

Rectal cancer is a heterogeneous disease at the genetic and molecular levels, both aspects having major repercussions on the tumor immune contexture. Whilst microsatellite status and tumor mutational load have been associated with response to immunotherapy, presence of tumor-infiltrating lymphocytes is one of the most powerful prognostic and predictive biomarkers. Yet, the majority of rectal cancers are characterized by microsatellite stability, low tumor mutational burden and poor T cell infiltration. Consequently, these tumors do not respond to immunotherapy and treatment largely relies on radiotherapy alone or in combination with chemotherapy followed by radical surgery. Importantly, pre-clinical and clinical studies suggest that radiotherapy can induce a complete reprograming of the tumor microenvironment, potentially sensitizing it for immune checkpoint inhibition. Nonetheless, growing evidence suggest that this synergistic effect strongly depends on radiotherapy dosing, fractionation and timing. Despite ongoing work, information about the radiotherapy regimen required to yield optimal clinical outcome when combined to checkpoint blockade remains largely unavailable. In this review, we describe the molecular and immune heterogeneity of rectal cancer and outline its prognostic value. In addition, we discuss the effect of radiotherapy on the tumor microenvironment, focusing on the mechanisms and benefits of its combination with immune checkpoint inhibitors.

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.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Early Progression ◽  
Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

Mature tertiary lymphoid structures in lung adenocarcinoma are associated with better progression free survival

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S149-S149
Author(s):  
R Obeng ◽  
V Parihar ◽  
D Alexis ◽  
M Behera ◽  
T Owonikoko ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Germinal Centers ◽  
Disease Stage ◽  
Free Survival ◽  
Formalin Fixed Paraffin Embedded ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Lymphoid Aggregates

Abstract Introduction/Objective The presence of inducible lymphoid structures known as tertiary lymphoid structures in the tumor microenvironment has been shown to correlate with positive clinical outcome. However, the maturation states of lymphoid aggregates in lung adenocarcinoma are not completely understood. Methods/Case Report Seventy tumor samples from 69 patients diagnosed with lung adenocarcinoma (Stages I to III) between 2013 and 2015 were included in the study. The presence and maturation states of the lymphoid structures within the tumors were evaluated by conventional and 26 samples were further analyzed by multiplexed immunohistochemistry of formalin fixed paraffin embedded tissues and then quantified. Mature lymphoid follicles containing germinal centers were identified by the presence of CD21+ and BCL-6+ cells in an organized configuration within tight clusters of T and B cells. Results (if a Case Study enter NA) Samples with fully mature lymphoid structures (germinal centers) had larger tumors and higher disease stage. The number of mature lymphoid structures correlated with the total number of lymphoid aggregates present in the tumor microenvironment. Additionally, tumor samples with ≥10 mature lymphoid structures had more primary follicles. While there was no difference in overall survival, progression free survival was significantly longer in patients who had ≥10 mature lymphoid structures in comparison with patients who had &lt;10 mature structures. Conclusion In conclusion, a spectrum of lymphoid aggregates in different stages of maturation are present in lung adenocarcinoma. An increase in the number of mature lymphoid structures may be associated with progression free survival in patients with lung adenocarcinoma.

Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies: A Pooled Analysis of Phase III Trials

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Elvire Pons-Tostivint ◽  
Aurélien Latouche ◽  
Pauline Vaflard ◽  
Francesco Ricci ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Durable Response ◽  
Free Survival ◽  
Drug Classes ◽  
Metastatic Setting ◽  
The Mean

PURPOSE Immune checkpoint inhibitors (ICIs) have been demonstrated to improve overall survival (OS) in several tumor types. Durable responses have been reported with these agents in patients with melanoma and lung cancer. We aimed to quantify the proportion of patients who experience durable responses on ICIs and to compare it with other drug classes. PATIENTS AND METHODS We retrieved published phase III randomized trials that included at least one ICI arm in the recurrent and/or metastatic setting. A durable response to treatment was defined as a progression-free survival that exceeded three times the median progression-free survival of the whole population. The proportion of patients who experienced an OS that exceeded two times the median OS of the whole patient population also was estimated. RESULTS Nineteen studies involving 11,640 patients treated in 42 treatment arms (26 ICI and 16 non-ICI arms) were included. The mean proportion of patients who experienced a durable response was 2.3 times higher in those treated with an ICI compared with those treated in the control arms (25% v 11%). Durable responses were more frequent in patients treated with anti–PD-1/PD-L1 agents than in patients treated with anti–CTLA-4 agents (28% v 18%). The mean proportion of patients who had an OS that exceeded two times the median OS was also higher in those treated with ICIs than in those treated in the control arms (30% v 23%). In multivariable analysis, the effects of treatment with anti–PD-1/PD-L1 agents and of first-line treatment were statistically associated with a higher mean proportion of durable responses. CONCLUSION Durable responses were more frequent in patients treated with ICIs, although they also occurred in patients treated with other drug classes.

Sign in / Sign up

Export Citation Format

Share Document