Tumor-infiltrating lymphocytes in the immunotherapy era

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Clinical success of cancer immune checkpoint blockade (ICB) has increased focus on tumor-infiltrating lymphocytes (TILs).
• TIL responses (T cells, NK cells, B cells) in the tumor microenvironment are linked to immunotherapy outcomes.
• TILs show prognostic benefits even in cancers with poor immunotherapy response.

Purpose of the Study:

• To review recent advances in understanding tumor-infiltrating lymphocyte (TIL) biology.
• To discuss the prognostic benefit and predictive value of TILs in cancer therapy.
• To explore the heterogeneity and conserved patterns of TILs across cancer types.

Main Methods:

• Analysis of gene expression profiles and clonality of tumor-infiltrating lymphocytes (TILs) using single-cell technologies.
• Review of existing literature on TIL biology, clinical outcomes, and immunotherapy response.
• Comparative analysis of TIL landscapes across different cancer types.

Main Results:

• Single-cell analysis reveals significant cellular heterogeneity and distinct immune activation/exhaustion states within TILs.
• Many TIL states are conserved across tumor types, correlating with broad clinical responses to immunotherapy.
• Discrepancies exist in immunotherapy response despite similar TIL landscapes, indicating complex tumor-immune interactions.

Conclusions:

• A holistic, single-cell level understanding of TILs is emerging, but biomarker discovery for response and prognosis is ongoing.
• TILs possess both prognostic and predictive value for cancer immunotherapy, though their precise roles are still being elucidated.
• Further research is needed to fully decipher the complex interplay between TILs and tumor immunity for personalized treatment strategies.