Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma.

Maibach, Fabienne; Sadozai, Hassan; Jafari, S. Morteza Seyed; Hunger, Robert E.; Schenk, Mirjam (2020). Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma. Frontiers in immunology, 11(2105), p. 2105. Frontiers Research Foundation 10.3389/fimmu.2020.02105

fimmu-11-02105.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

Recent breakthroughs in tumor immunotherapy such as immune checkpoint blockade (ICB) antibodies, have demonstrated the capacity of the immune system to fight cancer in a number of malignancies such as melanoma and lung cancer. The numbers, localization and phenotypes of tumor-infiltrating lymphocytes (TIL) are not only predictive of response to immunotherapy but also key modulators of disease progression. In this review, we focus on TIL profiling in cutaneous melanoma using histopathological approaches and highlight the observed prognostic value of the primary TIL subsets. The quantification of TIL in formalin-fixed tumor samples ranges from visual scoring of lymphocytic infiltrates in H&E to multiplex immunohistochemistry and immunofluorescence followed by enumeration using image analysis software. Nevertheless, TIL enumeration in the current literature primarily relies upon single marker immunohistochemistry analyses of major lymphocyte subsets such as conventional T cells (CD3, CD4, CD8), regulatory T cells (FOXP3) and B cells (CD20). We review key studies in the literature on associations between TIL subsets and patient survival. We also cover recent findings with respect to the existence of ectopic lymphoid aggregates found in the TME which are termed tertiary lymphoid structures (TLS) and are generally a positive prognostic feature. In addition to their prognostic significance, the existence of various TIL sub-populations has also been reported to predict a patient's response to ICB. Thus, the literature on the predictive potential of TIL subsets in melanoma patients receiving ICB has also been discussed. Finally, we describe recently developed state-of-the-art profiling approaches for tumor infiltrating immune cells such as digital pathology scoring algorithms (e.g., Immunoscore) and multiplex proteomics-based immunophenotyping platforms (e.g., imaging mass cytometry). Translating these novel technologies have the potential to revolutionize tumor immunopathology leading to altering our current understanding of cancer immunology and dramatically improving outcomes for patients.

Item Type:

Journal Article (Review Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Sadozai, Hassan Ahmed, Jafari, Morteza, Hunger, Robert, Schenk, Mirjam


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




Frontiers Research Foundation




Mirjam Schenk

Date Deposited:

12 Nov 2020 10:00

Last Modified:

02 Mar 2023 23:33

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

immunotherapy melanoma prognostic marker tertiary lymphoid structure tumor immunology and microenvironment tumor infiltrating lymphocyte





Actions (login required)

Edit item Edit item
Provide Feedback