The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

Tewari, Nilanjana; Zaitoun, Abed M.; Arora, Arvind; Madhusudan, Srinivasan; Ilyas, Mohammad; Lobo, Dileep N.

doi:10.1186/1471-2407-13-436

Cited by 72 publications

(71 citation statements)

References 32 publications

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“…12 Tewari et al evaluated the prognostic significance of CD3+, CD8+, and CD20+ TILs in 81 PDAC patients and found an association between high levels of CD3+ and CD20+ TILs and higher survival rates. 31 In another study, Ino et al found that patients with a high CD4+ T-cell count, high CD8+ T-cell count, and low Treg count (defined as values higher and lower than the median for tumor-infiltrating immune cells) had longer survival than those with a low CD4+ T-cell count, low CD8+ T-cell count, and high Treg count. 32 A growing body of evidence suggests that the TIL status in the residual tumor after neoadjuvant chemotherapy can predict clinical outcomes of breast cancer patients.…”

Section: Discussionmentioning

confidence: 97%

Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemotherapy

Nejati

Goldstein²,

Halperin³

et al. 2017

Pancreas

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Objectives To examine tumor infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy. Methods Intra-tumoral CD4+, CD8+, and FOXP3+ lymphocytes was examined by immunohistochemistry using a computer-assisted quantitative analysis in 136 PDAC patients who received neoadjuvant therapy and pancreaticoduodenectomy. The results were correlated with clinicopathologic parameters and survival. Results High CD4+ TILs in treated PDAC were associated with high CD8+ TILs (P = 0.003), differentiation (P = 0.04) and a lower frequency of recurrence (P = 0.02). Patients with high CD4+ TILs had longer disease-free survival (DFS) and overall survival (OS) than did patients with low CD4+ TILs (P < 0.01). The median OS of patients with a high CD8+/FOXP3+ lymphocyte ratio (39.5 [standard deviation, 6.1] months) was longer than that of patients with a low CD8+/FOXP3+ lymphocyte ratio (28.3 [standard deviation, 2.3] months; P=0.01). In multivariate analysis, high CD4+ TILs were an independent prognostic factor for DFS [Hazard ratio (HR): 0.49, 95% CI, 0.30–0.81; P = 0.005] and OS (HR, 0.54; 95% CI, 0.33–0.89; P = 0.02). Conclusions High CD4+ lymphocytes is associated with tumor differentiation, lower recurrence and is an independent prognostic factor for survival in PDAC patients treated with neoadjuvant therapy.

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Section: Discussionmentioning

confidence: 97%

Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemotherapy

Nejati

Goldstein²,

Halperin³

et al. 2017

Pancreas

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“…Improved prognosis was seen with high levels of infiltration by CD3 + , CD8 + or CD4 + T cells and CD20 + B cells [113–115]. Further histological characterization of the proposed immunogenic subtype of pancreatic ductal adenocarcinoma will be of value to inform forthcoming immunotherapy clinical trials.…”

Section: Tils In Upper Gastrointestinal Tract Carcinomasmentioning

confidence: 99%

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Hendry

Salgado

Gevaert

et al. 2017

Advances in Anatomic Pathology

611

366

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Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

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“…Not only is there increasing clinical evidence that infiltration of immune cells into the tumor is prognostically significant [136][137][138], but the avoidance of immune destruction is considered an emerging hallmark of cancer [139]. Current opinions suggest that there are at least two ways in which the immune system is involved in cancer.…”

Section: Regulatory Immune Cellsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

157

134

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The development of novel cancer therapeutics is often plagued by discrepancies between drug efficacies obtained in preclinical studies and outcomes of clinical trials. The inconsistencies can be attributed to a lack of clinical relevance of the cancer models used for drug testing. While commonly used in vitro culture systems are advantageous for addressing specific experimental questions, they are often gross, fidelity-lacking simplifications that largely ignore the heterogeneity of cancers as well as the complexity of the tumor microenvironment. Factors such as tumor architecture, interactions among cancer cells and between cancer and stromal cells, and an acidic tumor microenvironment are critical characteristics observed in patient-derived cancer xenograft models and in the clinic. By mimicking these crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic.

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The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays

Cited by 72 publications

References 32 publications

Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemotherapy

Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Chemotherapy

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

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