Editorial

5 pages, 386 KiB

Open AccessEditorial

External Quality Assessment 2.0: The Importance of a Standardized Implementation of TILs for Daily and Trial Practices

by Inne Nauwelaers, Nele Laudus, Dieter Peeters, Balazs Acs, Carsten Denkert, Stefan Michiels, Hugo Horlings, Kalliopi P. Siziopikou, Scott Ely, Dimitrios Zardavas, Roberts Mustimbo, John Bartlett, Giuseppe Floris, Johan Hartman, Carolien H. M. van Deurzen, Dorien Ceusters, Els Dequeker and Roberto Salgado

Cancers 2022, 14(15), 3762; https://doi.org/10.3390/cancers14153762 - 02 Aug 2022

Viewed by 1426

Abstract

Increasing data suggests that an intact immune system is required for improved
outcomes in patients with Human Epidermal Growth Factor Receptor 2 (HER2+) and Triple Negative Breast Cancer (TNBC) [...] Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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Research

Jump to: Editorial, Review

12 pages, 478 KiB

Open AccessArticle

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma

by Menekse Göker, Stephanie Deblaere, Hannelore Denys, Glenn Vergauwen, Eline Naert, Liv Veldeman, Chris Monten, Rudy Van den Broecke, Jo Van Dorpe, Geert Braems and Koen Van de Vijver

Cancers 2023, 15(11), 2894; https://doi.org/10.3390/cancers15112894 - 24 May 2023

Cited by 1 | Viewed by 1473

Abstract

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs and [...] Read more.

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area using the following cut-offs: 0%; <5%; 5–9%; and 10–50%. The PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections using SP142 and 22C3 antibodies. Results: A total of 82% of the sixty-six patients were hormone receptor positive and 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs (≥1%) were present in 64% of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of ≥1%, and using the 22C3 antibody, 28% had a positive PD-L1 score of ≥1. There was no correlation between sTILs or PD-L1 expression and tumor size, tumor grade, nodal status, expression of estrogen receptor (ER), or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression; however, this was not associated with a survival improvement. Additional large trials are needed to understand immune infiltration in lobular cancer, especially in the pleomorphic subtype. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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14 pages, 2454 KiB

Open AccessArticle

Development of Training Materials for Pathologists to Provide Machine Learning Validation Data of Tumor-Infiltrating Lymphocytes in Breast Cancer

by Victor Garcia, Katherine Elfer, Dieter J. E. Peeters, Anna Ehinger, Bruce Werness, Amy Ly, Xiaoxian Li, Matthew G. Hanna, Kim R. M. Blenman, Roberto Salgado and Brandon D. Gallas

Cancers 2022, 14(10), 2467; https://doi.org/10.3390/cancers14102467 - 17 May 2022

Cited by 6 | Viewed by 2358

Abstract

The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and [...] Read more.

The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer biopsy specimens. After completing the pilot study, we found notable variability in the sTILs estimates as well as inconsistencies and gaps in the provided training to pathologists. Using the pilot study data and an expert panel, we created custom training materials to improve pathologist annotation quality for the pivotal study. We categorized regions of interest (ROIs) based on their mean sTILs density and selected ROIs with the highest and lowest sTILs variability. In a series of eight one-hour sessions, the expert panel reviewed each ROI and provided verbal density estimates and comments on features that confounded the sTILs evaluation. We aggregated and shaped the comments to identify pitfalls and instructions to improve our training materials. From these selected ROIs, we created a training set and proficiency test set to improve pathologist training with the goal to improve data collection for the pivotal study. We are not exploring AI/ML performance in this paper. Instead, we are creating materials that will train crowd-sourced pathologists to be the reference standard in a pivotal study to create an AI/ML model validation dataset. The issues discussed here are also important for clinicians to understand about the evaluation of sTILs in clinical practice and can provide insight to developers of AI/ML models. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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24 pages, 3780 KiB

Open AccessEditor’s ChoiceArticle

Spatial Characterization of Tumor-Infiltrating Lymphocytes and Breast Cancer Progression

by Danielle J. Fassler, Luke A. Torre-Healy, Rajarsi Gupta, Alina M. Hamilton, Soma Kobayashi, Sarah C. Van Alsten, Yuwei Zhang, Tahsin Kurc, Richard A. Moffitt, Melissa A. Troester, Katherine A. Hoadley and Joel Saltz

Cancers 2022, 14(9), 2148; https://doi.org/10.3390/cancers14092148 - 26 Apr 2022

Cited by 23 | Viewed by 5431

Abstract

Tumor-infiltrating lymphocytes (TILs) have been established as a robust prognostic biomarker in breast cancer, with emerging utility in predicting treatment response in the adjuvant and neoadjuvant settings. In this study, the role of TILs in predicting overall survival and progression-free interval was evaluated [...] Read more.

Tumor-infiltrating lymphocytes (TILs) have been established as a robust prognostic biomarker in breast cancer, with emerging utility in predicting treatment response in the adjuvant and neoadjuvant settings. In this study, the role of TILs in predicting overall survival and progression-free interval was evaluated in two independent cohorts of breast cancer from the Cancer Genome Atlas (TCGA BRCA) and the Carolina Breast Cancer Study (UNC CBCS). We utilized machine learning and computer vision algorithms to characterize TIL infiltrates in digital whole-slide images (WSIs) of breast cancer stained with hematoxylin and eosin (H&E). Multiple parameters were used to characterize the global abundance and spatial features of TIL infiltrates. Univariate and multivariate analyses show that large aggregates of peritumoral and intratumoral TILs (forests) were associated with longer survival, whereas the absence of intratumoral TILs (deserts) is associated with increased risk of recurrence. Patients with two or more high-risk spatial features were associated with significantly shorter progression-free interval (PFI). This study demonstrates the practical utility of Pathomics in evaluating the clinical significance of the abundance and spatial patterns of distribution of TIL infiltrates as important biomarkers in breast cancer. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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20 pages, 1665 KiB

Open AccessArticle

Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

by Mieke R. Van Bockstal, Maxine Cooks, Iris Nederlof, Mariël Brinkhuis, Annemiek Dutman, Monique Koopmans, Loes Kooreman, Bert van der Vegt, Leon Verhoog, Celine Vreuls, Pieter Westenend, Marleen Kok, Paul J. van Diest, Inne Nauwelaers, Nele Laudus, Carsten Denkert, David Rimm, Kalliopi P. Siziopikou, Scott Ely, Dimitrios Zardavas, Mustimbo Roberts, Giuseppe Floris, Johan Hartman, Balazs Acs, Dieter Peeters, John M.S. Bartlett, Els Dequeker, Roberto Salgado, Fabiola Giudici, Stefan Michiels, Hugo Horlings and Carolien H. M. van Deurzen Show full author list Hide full author list

Cancers 2021, 13(19), 4910; https://doi.org/10.3390/cancers13194910 - 29 Sep 2021

Cited by 10 | Viewed by 3217

Abstract

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the [...] Read more.

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive vs. negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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Graphical abstract

16 pages, 1590 KiB

Open AccessArticle

Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer

by Darren Kilmartin, Mark O’Loughlin, Xavier Andreu, Zsuzsanna Bagó-Horváth, Simonetta Bianchi, Ewa Chmielik, Gábor Cserni, Paulo Figueiredo, Giuseppe Floris, Maria Pia Foschini, Anikó Kovács, Päivi Heikkilä, Janina Kulka, Anne-Vibeke Laenkholm, Inta Liepniece-Karele, Caterina Marchiò, Elena Provenzano, Peter Regitnig, Angelika Reiner, Aleš Ryška, Anna Sapino, Elisabeth Specht Stovgaard, Cecily Quinn, Vasiliki Zolota, Mark Webber, Davood Roshan, Sharon A. Glynn and Grace Callagy Show full author list Hide full author list

Cancers 2021, 13(17), 4410; https://doi.org/10.3390/cancers13174410 - 31 Aug 2021

Cited by 9 | Viewed by 2502

Abstract

Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This [...] Read more.

Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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8 pages, 572 KiB

Open AccessArticle

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

by Alhadi Almangush, Ibrahim O. Bello, Ilkka Heikkinen, Jaana Hagström, Caj Haglund, Luiz Paulo Kowalski, Ricardo D. Coletta, Antti A. Mäkitie, Tuula Salo and Ilmo Leivo

Cancers 2021, 13(13), 3235; https://doi.org/10.3390/cancers13133235 - 29 Jun 2021

Cited by 10 | Viewed by 1888

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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15 pages, 1615 KiB

Open AccessArticle

Automated Quantification of sTIL Density with H&E-Based Digital Image Analysis Has Prognostic Potential in Triple-Negative Breast Cancers

by Jeppe Thagaard, Elisabeth Specht Stovgaard, Line Grove Vognsen, Søren Hauberg, Anders Dahl, Thomas Ebstrup, Johan Doré, Rikke Egede Vincentz, Rikke Karlin Jepsen, Anne Roslind, Iben Kümler, Dorte Nielsen and Eva Balslev

Cancers 2021, 13(12), 3050; https://doi.org/10.3390/cancers13123050 - 18 Jun 2021

Cited by 18 | Viewed by 5167

Abstract

Triple-negative breast cancer (TNBC) is an aggressive and difficult-to-treat cancer type that represents approximately 15% of all breast cancers. Recently, stromal tumor-infiltrating lymphocytes (sTIL) resurfaced as a strong prognostic biomarker for overall survival (OS) for TNBC patients. Manual assessment has innate limitations that [...] Read more.

Triple-negative breast cancer (TNBC) is an aggressive and difficult-to-treat cancer type that represents approximately 15% of all breast cancers. Recently, stromal tumor-infiltrating lymphocytes (sTIL) resurfaced as a strong prognostic biomarker for overall survival (OS) for TNBC patients. Manual assessment has innate limitations that hinder clinical adoption, and the International Immuno-Oncology Biomarker Working Group (TIL-WG) has therefore envisioned that computational assessment of sTIL could overcome these limitations and recommended that any algorithm should follow the manual guidelines where appropriate. However, no existing studies capture all the concepts of the guideline or have shown the same prognostic evidence as manual assessment. In this study, we present a fully automated digital image analysis pipeline and demonstrate that our hematoxylin and eosin (H&E)-based pipeline can provide a quantitative and interpretable score that correlates with the manual pathologist-derived sTIL status, and importantly, can stratify a retrospective cohort into two significant distinct prognostic groups. We found our score to be prognostic for OS (HR: 0.81 CI: 0.72–0.92 p = 0.001) independent of age, tumor size, nodal status, and tumor type in statistical modeling. While prior studies have followed fragments of the TIL-WG guideline, our approach is the first to follow all complex aspects, where appropriate, supporting the TIL-WG vision of computational assessment of sTIL in the future clinical setting. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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Review

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23 pages, 5452 KiB

Open AccessReview

Comparative Evaluation of Tumor-Infiltrating Lymphocytes in Companion Animals: Immuno-Oncology as a Relevant Translational Model for Cancer Therapy

by Christopher J. Pinard, Andrew Lagree, Fang-I Lu, Jonathan Klein, Michelle L. Oblak, Roberto Salgado, Juan Carlos Pinto Cardenas, Barbara Brunetti, Luisa Vera Muscatello, Giuseppe Sarli, Maria Pia Foschini, Alexandros Hardas, Simon P. Castillo, Khalid AbdulJabbar, Yinyin Yuan, David A. Moore and William T. Tran

Cancers 2022, 14(20), 5008; https://doi.org/10.3390/cancers14205008 - 13 Oct 2022

Cited by 5 | Viewed by 4024

Abstract

Despite the important role of preclinical experiments to characterize tumor biology and molecular pathways, there are ongoing challenges to model the tumor microenvironment, specifically the dynamic interactions between tumor cells and immune infiltrates. Comprehensive models of host-tumor immune interactions will enhance the development [...] Read more.

Despite the important role of preclinical experiments to characterize tumor biology and molecular pathways, there are ongoing challenges to model the tumor microenvironment, specifically the dynamic interactions between tumor cells and immune infiltrates. Comprehensive models of host-tumor immune interactions will enhance the development of emerging treatment strategies, such as immunotherapies. Although in vitro and murine models are important for the early modelling of cancer and treatment-response mechanisms, comparative research studies involving veterinary oncology may bridge the translational pathway to human studies. The natural progression of several malignancies in animals exhibits similar pathogenesis to human cancers, and previous studies have shown a relevant and evaluable immune system. Veterinary oncologists working alongside oncologists and cancer researchers have the potential to advance discovery. Understanding the host-tumor-immune interactions can accelerate drug and biomarker discovery in a clinically relevant setting. This review presents discoveries in comparative immuno-oncology and implications to cancer therapy. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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28 pages, 15147 KiB

Open AccessReview

Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

by Isobelle Wall, Victoire Boulat, Aekta Shah, Kim R. M. Blenman, Yin Wu, Elena Alberts, Dinis Pedro Calado, Roberto Salgado and Anita Grigoriadis

Cancers 2022, 14(18), 4505; https://doi.org/10.3390/cancers14184505 - 17 Sep 2022

Cited by 3 | Viewed by 3607

Abstract

During the anti-tumour response to breast cancer, the primary tumour, the peripheral blood, and the lymph nodes each play unique roles. Immunological features at each site reveal evidence of continuous immune cross-talk between them before, during and after treatment. As such, immune responses [...] Read more.

During the anti-tumour response to breast cancer, the primary tumour, the peripheral blood, and the lymph nodes each play unique roles. Immunological features at each site reveal evidence of continuous immune cross-talk between them before, during and after treatment. As such, immune responses to breast cancer are found to be highly dynamic and truly systemic, integrating three distinct immune sites, complex cell-migration highways, as well as the temporal dimension of disease progression and treatment. In this review, we provide a connective summary of the dynamic immune environment triad of breast cancer. It is critical that future studies seek to establish dynamic immune profiles, constituting multiple sites, that capture the systemic immune response to breast cancer and define patient-selection parameters resulting in more significant overall responses and survival rates for breast cancer patients. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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15 pages, 701 KiB

Open AccessReview

The Significance of External Quality Assessment Schemes for Molecular Testing in Clinical Laboratories

by Nele Laudus, Lynn Nijs, Inne Nauwelaers and Elisabeth M. C. Dequeker

Cancers 2022, 14(15), 3686; https://doi.org/10.3390/cancers14153686 - 28 Jul 2022

Cited by 4 | Viewed by 3920

Abstract

External quality assessment (EQA) schemes are a tool for clinical laboratories to evaluate and manage the quality of laboratory practice with the support of an independent party (i.e., an EQA provider). Depending on the context, there are different types of EQA schemes available, [...] Read more.

External quality assessment (EQA) schemes are a tool for clinical laboratories to evaluate and manage the quality of laboratory practice with the support of an independent party (i.e., an EQA provider). Depending on the context, there are different types of EQA schemes available, as well as various EQA providers, each with its own field of expertise. In this review, an overview of the general requirements for EQA schemes and EQA providers based on international guidelines is provided. The clinical and scientific value of these kinds of schemes for clinical laboratories, clinicians and patients are highlighted, in addition to the support EQA can provide to other types of laboratories, e.g., laboratories affiliated to biotech companies. Finally, recent developments and challenges in laboratory medicine and quality management, for example, the introduction of artificial intelligence in the laboratory and the shift to a more individual-approach instead of a laboratory-focused approach, are discussed. EQA schemes should represent current laboratory practice as much as possible, which poses the need for EQA providers to introduce latest laboratory innovations in their schemes and to apply up-to-date guidelines. By incorporating these state-of-the-art techniques, EQA aims to contribute to continuous learning. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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12 pages, 1984 KiB

Open AccessReview

Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: Ready for Prime Time?

by Alhadi Almangush, Stijn De Keukeleire, Sylvie Rottey, Liesbeth Ferdinande, Tijl Vermassen, Ilmo Leivo and Antti A. Mäkitie

Cancers 2022, 14(6), 1558; https://doi.org/10.3390/cancers14061558 - 18 Mar 2022

Cited by 16 | Viewed by 3045

Abstract

The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now recommended in the classification of breast [...] Read more.

The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now recommended in the classification of breast tumors. Emerging evidence indicates that the significance of TILs extends to other cancer types, including head and neck cancer. In the era of immunotherapy as a treatment choice for head and neck cancer, assessment of TILs and immune checkpoints is of high clinical relevance. The availability of the standardized method from the International Immuno-oncology Biomarker Working Group (IIBWG) is an important cornerstone toward standardized assessment. The aim of the current article is to summarize the accumulated evidence and to establish a clear premise for future research toward the implementation of TILs in the personalized management of head and neck squamous cell carcinoma patients. Full article

(This article belongs to the Special Issue Tumor Infiltrating Lymphocytes (TIL) in Solid Tumors: Emerging Insights)

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