Tumor-infiltrating lymphocytes as a prognostic and predictive factor for Melanoma

ABSTRACT

Introduction

Tumor-infiltrating lymphocytes (TILs) have been investigated as prognostic factors in melanoma. Recent advancements in assessing the tumor microenvironment in the setting of more widespread use of immune checkpoint blockade have reignited interest in identifying predictive biomarkers. This review examines the function and significance of TILs in cutaneous melanoma, evaluating their potential as prognostic and predictive markers.

Areas covered

A literature search was conducted on papers covering tumor infiltrating lymphocytes in cutaneous melanoma available online in PubMed and Web of Science from inception to 1 December 2023, supplemented by citation searching. This article encompasses the assessment of TILs, the role of TILs in the immune microenvironment, TILs as a prognostic factor, TILs as a predictive factor for immunotherapy response, and clinical applications of TILs in the treatment of cutaneous melanoma.

Expert opinion

Tumor-infiltrating lymphocytes play a heterogeneous role in cutaneous melanoma. While they have historically been associated with improved survival, their status as independent prognostic or predictive factors remains uncertain. Novel methods of TIL assessment, such as determination of TIL subtypes and molecular signaling, demonstrate potential for predicting therapeutic response. Further, while their clinical utility in risk-stratification in melanoma treatment shows promise, a lack of consensus data hinders standardized application.

KEYWORDS:

• Immune checkpoint blockade
• immunotherapy
• melanoma
• prognostic factors
• sentinel lymph node biopsy
• TIL
• tumor-infiltrating lymphocytes

Article highlights

• TILs are lymphocytes that have infiltrated and disrupted tumor cells within a malignant lesion. TILs play a unique role within the tumor microenvironment of melanoma due to its strong immunogenicity.

• TIL grade is a standard component for pathology reports for melanoma specimen. Methods for detecting immune signaling protein expression can be used to further characterize the diverse role of TILs in the melanoma tumor microenvironment.

• Evidence in support of TILs as a prognostic factor for outcomes in melanoma is weaker than for other, validated prognostic factors for melanoma. However, TILs may be considered as an adjunct prognostic factor in clinical scenarios for which society guidelines are not prescriptive.

• TILs hold promise as a predictive factor for response to immunotherapy treatments for melanoma, but there is currently insufficient data to implement in a clinical setting at this time.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Notes

1. BRAF and NGS are not recommended for resected stage I-II cutaneous melanoma unless informing clinical trial participation. BRAF testing is recommended for stage III patients at high risk for recurrence for whom BRAF-directed therapy may be an option. Cases of stage IV disease or clinical recurrence should undergo testing for BRAF and other broad NGS panels when possible to guide treatment options.

2. PD-L1 is measured as a proportion of cells expressing PD-L1 via a variety of immunohistochemistry; different assays have not shown perfect concordance in measurement amongst one another.

Additional information

Funding

This paper was not funded.