scholarly journals The identification of tumor-infiltrating lymphocytes in patients with stomach cancer

2021 ◽  
Vol 23 (2) ◽  
pp. 307-312
Author(s):  
Gulnoz G. Khakimova ◽  
Yana A. Bozhchenko ◽  
Tatyana N. Zabotina ◽  
Alexey A. Tryakin
Keyword(s):  
Overall Survival ◽  
Stomach Cancer ◽  
Gastric Adenocarcinoma ◽  
Predictive Factors ◽  
Tnm Classification ◽  
Survival Rates ◽  
Tumor Infiltrating Lymphocytes ◽  
Spatial Location ◽  
Tumor Infiltration ◽  
Infiltrating Lymphocytes

Background. Stomach cancer (SC) is the 6th most common neoplasm among cancers (1 033 701 cases; 5.7%) and the 3rd most deadly cancer worldwide for men and women (782 685 deaths, 8.2%). SC therapy is a complex treatment associated with surgery, adjuvant chemotherapy, targeted therapy and immunotherapy with checkpoint inhibitors, nowadays. Despite the fact that the SC understanding has significantly increased within recent years, the prognosis still remains poor. In addition, very often the patients with the same stage of SC according to the international TNM classification of malignant tumors have different overall survival. Therefore, in order to improve survival rates, is necessary to understand the mechanisms of disease progression and to find new effective predictive factors. Besides many SC predictive factors, such as clinical and morphological characteristics (Lauren histologic type of tumor, degree of differentiation), biomarkers, deficient mismatch repair (dMMR), we have also revealed the positive correlation between the degree of tumor infiltration of tumor-infiltrating lymphocytes (TILs), especially with the spatial location of cell types (intratumoral or stromal cells), and the survival indicators of the patients with malignant neoplasms, recently. Moreover, TILs are the most significant predictive factors in patient survival rates than the TNM classification. At the same time, TILs predictive role in SC is still not clearly defined. Thus, the understanding of the degree of tumor infiltration of TILs depending on the spatial location would allow to determine the predictive significance, as well as to determine the direction of the immune reactions generating in patients with SC at the tissue level, depending on the risk and probability of progression. Aim. To study the predictive significance of intratumoral and stromal CD4+TILs, CD8+TILs and CD4+/CD8+TILs in patients with gastric adenocarcinoma. Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 patients with stages IIII, 20 patients with stage IV) received surgical/combined treatment or independent chemotherapy, respectively, at the Blokhin National Medical Research Center of Oncology. The histological material was carried out before the treatment. Intratumoral (iTILs) and stromal (sTILs) values of CD4+TILs, CD8+TILs, CD4/CD8+TILs and the predictive significance in respect of overall survival and progression-free survival (PFS) were studied. Results. During the observation period (16.46.2 months) CD4+/CD8+iTILs were factors of poor prognosis concerning PFS in patients of the first group (p=0.035; odds ratio OR 3.264, 95% confidence interval CI). We also identified the statistically significant decrease in CD4+iTILs, CD8+iTILs, CD4+/CD8+iTILs and the absence of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs in patients with metastatic SC (р=0.0003; р=0.000004; р=0.00001). Conclusion. The results show the positive predictive significance of CD4+sTILs, CD8+sTILs, CD4+/CD8+sTILs. At the same time, the increase of CD4+/CD8+iTILs reduces the PFS in patients with early and locally advanced SC.

scholarly journals Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3235
Author(s):  
Alhadi Almangush ◽  
Ibrahim O. Bello ◽  
Ilkka Heikkinen ◽  
Jaana Hagström ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tongue Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Staging System ◽  
Oral Tongue ◽  
Oral Tongue Cancer ◽  
Important Player ◽  
Infiltrating Lymphocytes

Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

scholarly journals Predicted CD4+ T cell infiltration levels could indicate better overall survival in sarcoma patients

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098153
Author(s):  
Qing Bi ◽  
Yang Liu ◽  
Tao Yuan ◽  
Huizhen Wang ◽  
Bin Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Survival Data ◽  
Tumor Infiltrating Lymphocytes ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Whole Exome ◽  
Cancer Genome Atlas ◽  
Infiltrating Lymphocytes

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

scholarly journals iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3276
Author(s):  
Alexandra Giatromanolaki ◽  
Avgi Tsolou ◽  
Eleftheria Daridou ◽  
Maria Kouroupi ◽  
Katerina Chlichlia ◽  
...  
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
Small Cell Lung Carcinoma ◽  
Expression Patterns ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tissue Samples ◽  
Cell Lung Carcinoma ◽  
Infiltrating Lymphocytes

Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia and anaerobic metabolism markers, PD-L1 and tumor-infiltrating lymphocytes (TILs). Results: iNOS is expressed by cancer cells in 19/98 (19.4%), while extensive expression by cancer-associated fibroblasts occurs in 8/98 (8.2%) cases. None of these patterns relate to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing TILs (iNOS+TILs) occurs in 47/98 (48%) cases. This is related to low Hypoxia-Inducible Factor 1α (HIF1α), high PD-L1 expression and a better overall survival (p = 0.002). Expression of PD-L1, however, mitigates the beneficial effect of the presence of iNOS+TIL. Conclusions: Extensive expression of iNOS by TILs occurs in approximately 50% of NSCLCs, and this is significantly related to an improved overall survival. This brings forward the role of iNOS in anti-neoplastic lymphocyte biology, supporting iNOS+TILs as a putative marker of immune response. The value of this biomarker as a predictive and treatment-guiding tool for tumor immunotherapy demands further investigation.

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.

scholarly journals Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

2019 ◽  
Vol 11 ◽  
pp. 175883591984887 ◽  
Author(s):  
Lorena Incorvaia ◽  
Giuseppe Badalamenti ◽  
Gaetana Rinaldi ◽  
Juan Lucio Iovanna ◽  
Daniel Olive ◽  
...  
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
Survival Rate ◽  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Primary Melanoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis.

Association of CDH1 mutation with prognosis in gastric adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15514-e15514
Author(s):  
Xiangyang Yu ◽  
Shimin Yang ◽  
Rong Du ◽  
Jingbo Zhang ◽  
Nan Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Stomach Cancer ◽  
Gastric Adenocarcinoma ◽  
Tumor Metastasis ◽  
Gene Mutations ◽  
Predictive Marker ◽  
Synonymous Mutations ◽  
Cdh1 Mutation ◽  
Gastric Cancer Patients

e15514 Background: Stomach cancer is a major cause of cancer death in East Asia. The purpose of this study was to find a predictive marker to estimate the prognosis of stomach cancer. Methods: In this study, a total of 34 gastric cancer patients receiving therapy in Tianjin Nankai Hospital were enrolled. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue sections, including carcinoma and pericarcinous tissues. Targeted regions of 549 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina Next-Seq 500 platform. Results: 25/34 patients had tumor metastasis. 135 non-silent mutations in 62 genes were detected in 27 tumor samples, while 7 patients’ samples had no mutation detected. CDH1, BRCA2 and SMAD4 gene mutations only occurred among metastasis patients. CDH1, BRCA2 and KRAS gene mutations are associated with a lower overall survival rate. Among them, 5 patients had a CDH1 mutation, including one splicing mutation, three frameshift mutations, one non-frameshift mutation and two non-synonymous mutations. All five patients had tumor metastasis, with the survival time less than 17 months, compared with all patients’ average overall survival of 22 month. Conclusions: Previous studies showed that mutation in CDH1 is linked to gastric cancer (GC) susceptibility and tumor invasion. Our results indicated that the mutation of CDH1 was also associated with the prognosis of gastric adenocarcinoma (P < .01) and was an independent factor (P < .05).

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.

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