TILs attacking cancer cells

TILs: A Personalized Approach to Conquering Breast Cancer

Rhea Morgan in Health & Wellness August 2025 • 4 min read.

"A breakthrough in adoptive immunotherapy offers new hope for patients with metastatic breast cancer resistant to conventional treatments."

Breast cancer, especially in its metastatic form, remains a significant challenge despite advancements in treatment. When standard therapies like chemotherapy fail, the need for innovative approaches becomes critical.

Now, research published in Nature Medicine highlights a promising avenue: adoptive immunotherapy using tumor-infiltrating lymphocytes (TILs). This personalized approach has shown remarkable success in a patient with metastatic ER+HER2- breast cancer that had become resistant to chemotherapy.

This article explores how this groundbreaking treatment works, why it's so effective, and what it means for the future of cancer therapy.

How Personalized TIL Therapy Works

The approach, led by Feldman and colleagues, centers around harnessing the power of the patient's own immune system to fight the cancer. Here's a breakdown of the key steps:

First, whole-exome sequencing of the tumor is performed. This process identifies the unique mutations present in the tumor cells, revealing potential targets for the immune system.

TIL Extraction and Expansion: Tumor-infiltrating lymphocytes (TILs) are extracted from the patient's tumor tissue. These are immune cells that have already recognized and infiltrated the tumor.
Ex Vivo Expansion: The extracted TILs are expanded in the laboratory (ex vivo) to generate a large population of cells capable of mounting a strong attack against the tumor. In this case, over 80 billion TILs were grown.
Re-infusion and Immune Boost: The expanded TILs are then re-infused back into the patient. This is often combined with treatments like IL-2 (a cytokine that boosts immune cell activity) and pembrolizumab (an antibody that blocks the PD-1 co-inhibitory molecule, unleashing the T cells' killing potential).
Neoantigen Recognition: Researchers identified that eleven clonotypes of the re-infused TILs recognized four different tumor neoantigens. Notably, these TILs persisted long-term in the patient, for at least 17 months.

The therapy resulted in the resolution of all tumor lesions within a year of TIL infusion, and the patient remained clear of cancer for over 22 months. This outcome highlights the profound impact of this personalized approach.

The Future of Cancer Treatment: Personalized Immunotherapy

This case demonstrates the remarkable potential of personalized TIL adoptive-transfer in achieving beneficial results for patients with advanced cancer. By tailoring the treatment to the individual's specific tumor mutations and immune response, this approach overcomes the limitations of traditional therapies.

While this is a single case study, it provides a strong rationale for further research and clinical trials to explore the efficacy of TIL therapy in a broader range of cancers and patient populations.

As our understanding of the immune system and tumor biology deepens, personalized immunotherapy approaches like TIL therapy are poised to revolutionize cancer treatment, offering hope for durable remissions and improved outcomes.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1038/s41590-018-0175-2, Alternate LINK

Title: Tils Show The Way

Subject: Immunology

Journal: Nature Immunology

Publisher: Springer Science and Business Media LLC

Authors: Zoltan Fehervari

Published: 2018-07-19

Everything You Need To Know

What exactly are Tumor-Infiltrating Lymphocytes (TILs), and how are they used in personalized cancer treatment?

TILs, or Tumor-Infiltrating Lymphocytes, are immune cells that have already recognized and infiltrated a tumor. In personalized TIL therapy, these cells are extracted from a patient's tumor tissue, expanded in the laboratory to create a large population, and then re-infused back into the patient to target and destroy the cancer cells. This process leverages the patient's own immune system to fight the cancer.

Can you explain the process of personalized TIL therapy from tumor sequencing to T-cell infusion?

Personalized TIL therapy involves several key steps, beginning with whole-exome sequencing of the tumor to identify unique mutations. Next, Tumor-Infiltrating Lymphocytes are extracted and expanded ex vivo to create a large population of cells. These expanded TILs are then re-infused back into the patient, often combined with treatments like IL-2 and pembrolizumab to boost immune cell activity and unleash the T cells' killing potential. Finally, these TILs recognize tumor neoantigens, leading to the destruction of cancer cells.

What are the implications of TIL therapy for patients with metastatic breast cancer who have not responded to traditional treatments?

The success of personalized TIL therapy in treating metastatic ER+HER2- breast cancer offers hope for patients who have developed resistance to standard treatments like chemotherapy. By tailoring the treatment to the individual's specific tumor mutations and immune response, this approach overcomes the limitations of traditional therapies. This has implications of potentially overcoming treatment resistance. While this approach is promising, it is important to note that it has been demonstrated in a single patient, and further research is necessary to determine its broad applicability.

What is the role of IL-2 and Pembrolizumab in Personalized TIL therapy, and how do they improve the treatment's effectiveness?

IL-2, or Interleukin-2, is a cytokine that plays a crucial role in boosting immune cell activity. In personalized TIL therapy, IL-2 is often administered alongside the re-infused TILs to enhance their ability to target and destroy cancer cells. Pembrolizumab is an antibody that blocks the PD-1 co-inhibitory molecule, unleashing the T cells' killing potential. The inclusion of IL-2 in the treatment regimen helps to amplify the immune response and improve the overall effectiveness of the therapy.

How do neoantigens contribute to the success of personalized TIL therapy in targeting and eliminating cancer cells?

Neoantigens are unique mutations present in tumor cells that can be recognized by the immune system. In the case of personalized TIL therapy, researchers identified that eleven clonotypes of the re-infused TILs recognized four different tumor neoantigens. This recognition is crucial for the TILs to specifically target and destroy the cancer cells, leading to the resolution of tumor lesions. The ability of TILs to recognize and target these neoantigens highlights the potential of personalized immunotherapy in achieving beneficial results for patients with advanced cancer.