Tumor-infiltrating lymphocytes
Tumor-infiltrating lymphocytes, also tumour infiltrating lymphocytes, are white blood cells that have left the bloodstream and migrated into a tumor. They are mononuclear immune cells, a mix of different types of cells (i.e., T cells, B cells, NK cells, macrophages) in variable proportions, T cells being the most abundant cells.[1]
They can often be found in the stroma and within the tumour itself.[1]
TILs are implicated in killing tumor cells. The presence of lymphocytes in tumors is often associated with better clinical outcomes.[2][3][4]
Contents
Detection and characteristics
When TILs are present the lymphocytes are found between the tumor cells; cells in the stroma surrounding the tumor cells do not count.[5] It should be noted that histologic definitions for TILs vary.
CD3 has been used to detect lymphocytes in tumor samples.[4]
Associations with cancer prognosis
Colorectal cancer
In colorectal cancer, they are associated with microsatellite instability cancers, as may be seen in Lynch syndrome.[6]
TILs are needed for checkpoint inhibitor therapy to work in GI cancers.[4]
Melanoma
They are an important prognostic factor in melanoma and higher levels being associated with a better outcome.[7][8]
Use in an autologous cell therapy
They are key to an experimental autologous cell therapy (Contego) for metastatic melanoma.[9]
Use as an adoptive cell transfer therapy
History
The use of TILs as an adoptive cell transfer therapy to treat cancer was pioneered by Dr. Steven Rosenberg at the National Cancer Institute.[citation needed] Autologous lymphocytes are isolated from patients’ tumors and cultured to large numbers of cells in vitro. Prior to TIL treatment, patients are given nonmyeloablative chemotherapy to deplete native lymphocytes that can inhibit the response. Once lymphodepletion is completed, patients are infused with TILs in combination with interleukin 2 (IL-2). Lion Biotechnologies is developing adoptive cell transfer with TILs as a cancer therapy.
for Melanoma
Several centres are currently working on TIL melanoma treatment protocol, including the Ella Institute in Sheba Hospital, Israel[10] and Copenhagen University Hospital at Herlev, Denmark [11][12]
Clinical trials have used TILs to treat patients with metastatic melanoma. Tumor reduction of 50% or more was observed in about half of patients.[13][14][15][16] Some patients experienced complete responses with no detectable tumor remaining years after treatment.[17]
for Other cancers
Clinical trials using TILs to treat digestive tract cancers, such as colorectal cancer,[18] and cancers associated with the human papilloma virus (HPV), such as cervical cancer,[19] are ongoing.
Under investigation are the use of TILs to treat other tumors, including lung, ovarian, bladder, and breast.
See also
References
- ↑ 1.0 1.1 Breast Cancer Immunology. Oncology Times: 10 May 2016 - Volume 38 - Issue 9 - p 18–19 doi: 10.1097/01.COT.0000483221.52404.e3
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- ↑ 4.0 4.1 4.2 Immunotherapy Doubts Fading in GI Cancers. April 2016
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- ↑ Clinical trial number NCT01174121 for "A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers" at ClinicalTrials.gov
- ↑ Clinical trial number NCT01585428 for "A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers" at ClinicalTrials.gov
External links
- Tumor infiltrating lymphocyte entry in the public domain NCI Dictionary of Cancer Terms
- Lion Biotechnologies, Inc.
