scholarly journals Tumor-Infiltrating Lymphocytes and Cancer Markers in Osteosarcoma: Influence on Patient Survival

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6075
Author(s):  
José Manuel Casanova ◽  
Jani-Sofia Almeida ◽  
John David Reith ◽  
Luana Madalena Sousa ◽  
Ruben Fonseca ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cells ◽  
Strong Association ◽  
Tumor Biology ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Cd4 Cells ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Osteosarcoma (OST) is the most common type of high-grade primary bone tumor, which mainly affects young adults. The current standard of care for OST combines surgical resection with chemotherapy. The clinical outcomes and the current options to treat OST patients are unsatisfactory and novel treatment strategies are needed. The crosstalk between tumor cells and immune cells is essential to the OST microenvironment. Despite the efforts that have been made to address the importance of immune-related factors in OST, there is still a lot to understand. The purpose of the current study was to evaluate the tumor-infiltrating lymphocytes (TIL), the expression of proteins involved in tumor biology, and their impact on the clinical outcome of OST patients. We studied 93 samples of OST patients using immunohistochemistry and histomorphometry. We looked for the infiltration of CD3+, CD4+, CD8+, TIA1+ and CD20+ cells and for the expression of CD44 standard (CD44s) and variant 6 (CD44v6), CD95/Fas, Fas-L, p53 and p-glycoprotein. All the parameters were analyzed for the influence on the occurrence of death and metastasis, plus patient overall survival (OS) and progression-free survival (PFS). The effect of sex, age, tumor location (distal femur or proximal tibia) and the combination with neoadjuvant chemotherapy was also assessed. Our results suggest that the presence of tumor-infiltrating CD4+ cells provides protection to OST patients, and that CD8+ cells have a significant impact on the patient’s overall survival (OS) and progression-free survival (PFS), which is more evident in male patients. In addition, a strong association between tumor-infiltrating CD4+ cells and the presence of CD44s expression in tumor samples was observed. Analysis of TIL and tumor markers related to tumor biology could be useful to stratify patients and monitor the response to therapy, as well as to assist with the development of immunotherapy strategies to improve the effects of cytotoxic TIL to eradicate the tumor cells.

scholarly journals Intratumoral immune cells expressing PD-1/PD-L1 and their prognostic implications in cancer: a meta-analysis

2018 ◽  
Vol 33 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Younghoon Kim ◽  
Xianyu Wen ◽  
Nam Yun Cho ◽  
Gyeong Hoon Kang
Keyword(s):  
Overall Survival ◽  
Immune Cells ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
Tissue Sections ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Background: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. Methods: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival. Subgroup analysis was based on the tissue type of cancer and the type of tissue sampling (tissue microarray or whole tissue section). Results: In the meta-analysis, PD-1-positive and PD-L1-positive tumor-infiltrating lymphocytes had a positive effect on disease-free survival or progression-free survival (hazard ratio [HR] 0.732; 95% confidence interval [CI] 0.565, 0.947; and HR 0.727; 95% CI 0.584, 0.905, respectively). PD-L1-positive tumor-infiltrating lymphocytes had a positive impact on overall survival in studies using tissue microarray (HR 0.586; 95% CI 0.476, 0.721), but had a poor impact when only whole tissue sections were considered (HR 1.558; 95% CI 1.232, 1.969). Lung cancer was associated with good overall survival and disease-free survival (HR 0.639; 95% CI 0.491, 0.831; and HR 0.693; 95% CI 0.538, 0.891, respectively) for PD-1-positive tumor-infiltrating lymphocytes, and colorectal cancer showed favorable disease-free survival (HR 0.471; 95% CI 0.308, 0.722) for PD-L1-positive tumor-infiltrating lymphocytes. Conclusion: Immune cells expressing PD-1 and PD-L1 within tumors are associated with the prognosis. However, the correlation may vary among different tumor types and by the type of tissue sampling used for the assessment.

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas

2021 ◽  
pp. 021849232110421
Author(s):  
Mona Mlika ◽  
Ayoub Saidi ◽  
Nesrine Mejri ◽  
Mehdi Abdennadher ◽  
Chokri Haddouchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Lung Carcinomas ◽  
Forkhead Box ◽  
Infiltrating Lymphocytes

Introduction Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. Methods We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. Results Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p = 0.009), and a CD8/CD4 ratio ( p = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p = 0.003), the forkhead box protein P3/CD8 ( p = 0.005), and forkhead box protein P3/CD4 ( p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p = 0.004) and a CD8/CD4 ratio ( p = 0.016) were independent predictors of overall survival. Conclusion Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

Treatment with tumor-infiltrating lymphocytes in the changing treatment landscape of metastatic melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14024-e14024 ◽  
Author(s):  
Troels Borch ◽  
Rikke Andersen ◽  
Eva Ellebaek ◽  
Özcan Met ◽  
Marco Donia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Median Overall Survival ◽  
Adoptive Cell Therapy ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Subsequent Treatment ◽  
Clinical Response Rate ◽  
Previously Treated ◽  
Infiltrating Lymphocytes

e14024 Background: Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has been shown to induce durable complete responses in patients with metastatic melanoma (MM) who are anti-PD-1 naïve. Whether progression on or after anti-PD-1 therapy affects the outcome of TIL therapy given as a subsequent treatment line is largely unknown. To elucidate this, we analyzed updated clinical data covering a decade of TIL trials carried out in Denmark. Methods: Data from three clinical trials were pooled and data from 55 treated patients were available (ClinicalTrials.gov Identifiers: NCT00937625 (n = 31), NCT02379195 (n = 12) and NCT02354690 (n = 12)). Survival curves were computed according to the Kaplan-Meier method. Clinical response rate (RR) was evaluated according to RECIST criteria. Results: Median overall survival in the pooled cohort was 15.9 months and progression-free survival (PFS) was 3.7 months. Six patients achieved a complete response (11%), of which four are ongoing. Fourteen patients achieved a partial response (26%), of which three are ongoing. Median overall survival of responders was not reached with a median follow-up time of 40 months. RR was not statistically different depending on prior anti-PD-1 therapy (42% no prior anti-PD-1 therapy vs. 32% with prior anti-PD-1 therapy). However, there was a trend towards a shorter duration of partial responses in patients previously treated with both anti-CTLA-4 monotherapy and anti-PD-1 monotherapy, compared to patients previously treated with anti-CTLA-4 but not anti-PD-1 (P = 0.06). The two groups were balanced in respect to number of prior treatment lines. Conclusions: After progression on anti-PD-1 therapy, partial responses following TIL therapy might be shorter, but durable complete responses can be induced despite progression on prior anti-PD-1 therapy. Thus, TIL therapy remains an important treatment strategy in MM. Clinical trial information: NCT00937625, NCT02379195, NCT02354690.

Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas—A two-center phase II trial (GBFiri)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14088-14088
Author(s):  
J. Feisthammel ◽  
K. Schoppmeyer ◽  
M. Wiedmann ◽  
J. Mossner ◽  
M. Schulze ◽  
...  
Keyword(s):  
Overall Survival ◽  
Folinic Acid ◽  
Biliary Tract ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Synergistic Activity ◽  
Biliary Cancer ◽  
Free Survival

14088 Background: The majority of patients with biliary tract cancer present with advanced, unresectable tumors. Irinotecan and 5-Fluorouracil/folinic acid (FOLFIRI) have synergistic activity in gastrointestinal cancers. The aim of this study was to determine the tolerability and activity of systemic chemotherapy with FOLFIRI in patients with intrahepatic cholangiocarcinoma (CCC) or gallbladder cancer (GBC). Methods: This was a prospective, multicenter, non-randomised, open-label, phase II trial. Eligibility criteria: Inoperable adenocarcinoma of the biliary tract, measurable disease, age 18–80 years, ECOG PS 0–2. Patients received irinotecan 80 mg/m2 as a 30 min infusion, followed by folinic acid 500 mg/m2 over 2 h and 5-FU 2000 mg/m2 over 24h weekly × 6 followed by a 2 week rest. Treatment was continued until progression or limiting toxicity. Response to therapy was assessed after every other cycle according to RECIST criteria. Primary end point was response rate, secondary end points were overall survival, progression free survival and toxicity. Results: 30 pts (CCC 17, GBC 13) were enrolled. A total of 387 doses (Median 12.9; 1 to 36) were administered with an overall relative dose intensity of 98%. 30 patients are evaluable for safety. WHO grade 3/4 drug related adverse events occured in 7 patients (23%): Leukopenias in 2, anemia in 1, and diarrhea in 4 patients. 14 patients completed 2 cycles and were evaluable for response. Response rates: CR 0/30, PR 3/30 (10%) and SD 3/30 (10%). 8 patients presented with disease progression at restaging. Median overall survival: CCC 166 days, GBC 327 days. Progression-free-survival: CCC 84 days, GBC 159 days. Conclusions: FOLFIRI is a well tolerated regimen in patients with biliary cancer that can be safely administered on an outpatient basis. FOLFIRI has no substantial activity in CCC and moderate activity in GBC. Further studies are required to define a standard palliative chemotherapy for treatment of biliary cancer. No significant financial relationships to disclose.

Effect of baseline carbohydrate antigen 19-9 (CA19-9) level on overall survival (OS) in NAPOLI-1 trial: A phase III study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Li-Tzong Chen ◽  
Jens T Siveke ◽  
Andrea Wang-Gillam ◽  
Richard Hubner ◽  
Shubham Pant ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Effect ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
Phase Iii ◽  
Free Survival ◽  
Previously Treated

425 Background: CA19-9 has been shown to correlate with response to therapy and OS in patients with mPAC. NAPOLI-1, a randomized phase 3 study evaluated nal-IRI, a nanoliposomal formulation of irinotecan, with or without 5-FU/LV vs 5-FU/LV in patients with mPAC previously treated with gemcitabine-based therapy. Nal-IRI+5-FU/LV significantly improved OS (primary endpoint) vs 5-FU/LV (6.1 mo vs 4.2 mo; unstratified hazard ratio [HR] = 0.67; P = 0.012). CA19-9 response (≥50% decline from baseline) was superior with nal-IRI+5FU/LV compared with 5-FU/LV (29% vs 9%; P=0.0006). Nal-IRI alone did not show a statistical improvement in survival. Methods: Patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 from nal-IRI+5-FU/LV and 5-FU/LV arms. Quartile ranges were based on 404 available CA19-9 values from randomized patients (N=417). Unstratified Cox proportional hazards regression was used to estimate HRs and corresponding 95% CIs. Effect of baseline CA19-9 on time to response, progression-free survival, and response will be presented. Results: Of patients randomized to receive nal-IRI+5-FU/LV (n = 117) or 5-FU/LV enrolled contemporaneously (n = 119), 218 received study drug and had a baseline CA19-9 measurement. Results show a greater treatment effect on OS with higher CA19-9 level relative to 5-FU/LV. Conclusions: In patients with mPAC previously treated with gemcitabine-based therapy, nal-IRI+5-FU/LV significantly improved OS supported by progression free survival and objective response rate. The CA19-9 serum level can provide important information with regards to overall survival. Clinical trial information: NCT01494506. [Table: see text]

scholarly journals Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110342
Author(s):  
Birhanu Aberha Berele ◽  
Yuxiang Cai ◽  
Guifang Yang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cd4 Cells ◽  
Free Survival ◽  
Registration Number ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objective: To evaluate the prognostic value of tumor infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) patients. Method: Meta-analysis was performed on eligible studies that was identified by systematic searching of Google scholar, MEDLINE, CNKI, Scopus, PubMed, PMC, Embase and Web of Science databases. The study protocol was registered in International Platform of Registered Systematic Review and Meta-Analysis Protocols-INPLASY (registration number: INPLASY202160014). Databases were searched from inception to January 20, 2020 to identify eligible studies. Those studies that evaluated survival in the form of hazard ratio (HR) in TILs of NPC patients was analyzed. All statistical analysis was performed by using STATA version 16.0 software. Result: Fourteen studies with a total of 3025 patients was analyzed. The pooled result showed that high TILs was significantly associated with favorable overall survival (OS) (HR = 0.55; 95%CI = 0.39-0.77; P = 0.001) and disease free survival (DFS) (HR = 0.60; 95%CI = 0.44-0.81; P = 0.04). Interestingly, high intratumoral TILs had relatively better OS (HR = 0.45; 95%CI = 0.35-0.58; P = 0.006) than stromal TILs (HR = 0.59; 95%CI = 0.36-0.97; P = 0.03). Moreover, an increased level of CD4+ cells infiltration was correlated with favorable OS (HR = 0.4; 95%CI = 0.18-0.85; P = 0.01). CD3+, CD8+ and FoxP3+ lymphocyte’s better prognosis was not statistically significant for OS ( P = 0.09; P = 0.07; P = 0.52) and for DFS ( P = 0.13; P = 0.29) respectively. However, subgroup analysis of intratumoral CD3+ (HR = 0.48; 95%CI = 0.33-0.70; P = 0.05) and intratumoral CD8+ (HR = 0.32; 95%CI = 0.16-0.62; P = 0.001) was significantly associated with improved OS, but not significant in stromal CD3+ (HR = 0.66; 95%CI = 0.20-2.20; P = 0.62). Conclusion: TILs were variably correlated with better prognosis depending on their microanatomic location and subset of TILs in NPC patients. CD4+, intratumoral CD3+ and intratumoral CD8+ lymphocytes could predict favorable patient outcome which suggest that their role in mediating antitumor immune response could potentially be exploited in the treatment of NPC patients. Future large study on the prognostic value of microanatomic location of TILs is needed for confirmation.

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