Are tumor-infiltrating lymphocytes protagonists or background actors in patient selection for cancer immunotherapy?

ABSTRACT

Introduction: Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of ‘“cancer immunoediting”’. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response.

Areas covered: In this review, the authors summarize the most relevant knowledge related to TILs. This includes their prognostic and predictive significance in various types of tumour and the recent findings about their potential role in the cancer immunotherapy.

Expert opinion: TILs evaluation could lead to a predictive biomarker for immunotherapy effectiveness in several cancer types. Furthermore, typing of TILs subpopulation could have clinical relevance in patient selection for treatment with immune checkpoint inhibitors. However further studies are still needed.

KEYWORDS:

• Immunotherapy
• immune checkpoint inhibitors
• microenvironment
• multiplex immunohistochemical
• programmed death 1
• Tumor-infiltrating lymphocytes

Article highlights

• TILs play a crucial role in many different cancers as a prognostic biomarker, generally associated with a favorable disease outcome.

• TILs might predict the response to both neoadjuvant and adjuvant chemotherapies in several cancers, proving their use in improving the handling of patients with various cancer types.

• TILs baseline density, location and subpopulation might substantially affect the clinical efficacy of the therapy targeting immune checkpoint inhibitors, suggesting their possible utility in patients’ selection for cancer immunotherapy.

• The tumors subtyping based on PD-L1 status and TILs presence could implement the identification of responders to anti-PD1/PD-L1 treatment, possibly leading to a tailored cancer immunotherapy.

• TILs evaluation should include the characterization of subpopulations to better identify patients who will be potential responders. Thus, multispectral immunohistochemical analysis could give a better characterization of the microenvironment associated to immune checkpoint, especially with the PD1/PD-L1 pathway.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Tom Nevin for editing the language of this paper.

Declaration of interest

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.

Additional information

Funding

This work is supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) while Federica Zito Marino is a recipient of an AIRC fellowship (Project IG 2013 N.14425).