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Tumor-Infiltrating Lymphocytes in the Checkpoint Inhibitor Era

  • Gerald P. LinetteEmail author
  • Beatriz M. Carreno
CART and Immunotherapy (M Ruella and P Hanley, Section Editors)
Part of the following topical collections:
  1. Topical Collection on CART and Immunotherapy

Abstract

Purpose of Review

Checkpoint inhibitors block co-inhibitory signals which serves to promote T cell activation/reinvigoration in the periphery and tumor microenvironment. A brief historical background as well as a summary of key observations related to the composition and prognostic value of tumor-infiltrating lymphocytes (TILs) is discussed.

Recent Findings

Solid tumor patients that respond to checkpoint inhibitors have greater CD8+ T cell densities (at the tumor margin) associated with a gene inflammation signature and high tumor mutational burden. The precise specificity of effector (CD8+ T cell) TIL remains poorly defined and this deficiency represents a major challenge for the field of cancer immunology.

Summary

High mutational burden cancers such as melanoma provides compelling evidence that missense mutations create neoantigens which can serve as target antigens for the immune system. Emerging evidence suggests that neoantigen-specific TILs are the major effector cells that mediate tumor regression due to checkpoint inhibition.

Keywords

Immunotherapy Neoantigens Cell therapy Melanoma Checkpoint inhibitor 

Notes

Funding Information

GPL and BMC are financially supported by CA204261, CA205794, CA217805, and the Abramson Cancer Center Translational Research Pilot Award.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article contains no studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for Cellular Immunotherapies and the Parker Institute for Cancer ImmunotherapyPhiladelphiaUSA
  2. 2.Department of Medicine, Division of Hematology-OncologyUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Pathology and Laboratory Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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