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

Abstract

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, gynecologic 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.

Figure 1

Applying the proposed standardized methodology to evaluate TILs in melanoma. Although traditional scoring systems have only considered intra-tumoral TILs in melanoma, both stromal and intra-tumoral TILs may be evaluated in the research setting. Areas of necrosis or ulceration are excluded.

Figure 2

When assessing TILs in non-small cell lung carcinoma, include lymphocytes in the fibrovascular cores of papillary structures (marked sTILs), and exclude alveolar macrophages.

Figure 3

An example of an ultramutated endometrial carcinoma with POLE mutation. Characteristic histological features include expansile growth with a pushing border, solid areas and serous-like morphology (panel A), as well as high FIGO grade and prominent stromal and intra-tumoral lymphoid infiltrate (panel B).

Figure 4

Examples of a range of stromal TILs percentages in high-grade serous ovarian carcinoma.