What are Tumor Infiltrating Lymphocytes (TIL)?

Tumor-infiltrating lymphocytes are white blood cells that have left the blood and are embedded in the tumor. Tumor mass comprises tumor cells in addition to stromal cells that enable tumors to grow and expand, endothelial cells, leukocytes, fibroblasts and a complex extracellular matrix (ECM). Together these cells form the tumor microenvironment (TME).

TILs are polymorphic and contain various populations of immune cells such as T cells, NK cells, dendritic cells and macrophages. TILs directly surround the tumors within the tumor stroma.

Why are TILs important in cancer immunotherapy?

The presence of TIL in the tumor bed has shown significance as a prognostic marker for cancer progression. The density of TIL infiltration has led to the classification of TIL in diseases such as melanoma. The most applied grading system for assessing TILs uses three grades:

  • Absent TIL infiltrate lymphocytes are either not present or, if present, they do not directly oppose tumor cells. It is not uncommon, for example, to see a cuff of lymphocytes around the periphery of a tumor or adjacent vascular spaces with no infiltration into the tumor itself. This is regarded as absent TILs.
  • A non-brisk TIL infiltrate is defined as a focal TIL infiltrate within the tumor that may be isolated, segmental, or multifocal.
  • A brisk TIL infiltrate is defined as the presence of either diffuse permeation of the tumor by TILs or a TIL infiltrate across the entire base of the tumor

Implications of TILs in Melanoma

Melanoma is considered an immunogenic malignancy containing various immune cells and subsets of T cell, dendritic cells, macrophages, neutrophils, B cells etc., Several studies have shown the histopathological influence of immune cells on melanoma progression. Multiple clinical research studies have also shown the presence of dense TIL is associated with favorable prognosis.

Analyzing the interactions of TILs and melanoma tumors in the TME have yielded promising therapeutic targets and biomarkers.

TIL 2164 and Tumor 2164 (melanoma)

TIL 2164 and Tumor 2164 is an autologous pairing obtained from a patient that did not respond to Keytruda (anti-PD1) treatment.

 

Internal characterization

We have further characterized TIL 2164 and tumor 2164 for expression of key markers. These include but not limited to:

Assays conducted to date:

  • Comparative studies using Keytruda (anti-PD-1) to measure tumor lysis
  • Comparative studies using Yervoy (anti-CTLA4)
  • Effect of drug candidate(s) on TIL 2164 migration in 3D co-cultures towards Tumor 2164
  • Characterization of immune sub-populations present in TIL 2164 in response to drug treatment
  • Immunosuppressive studies using allogeneic Tregs and Macrophages on CTL 020 inhibition of tumor 020 lysis
  • M1/M2 macrophage differentiation from TIL 2164

TIL 2265 and Tumor 2265 (melanoma)

TIL 2265 and Tumor 2265 is an autologous pairing obtained from a patient that was treated with Keytruda (anti-PD1) treatment.

 

Internal characterization

We have further characterized TIL 2265  and tumor 2265 for expression of key markers. These include but not limited to:

We have additional markers characterized and can work with clients in determining the expression of certain targets

 

Studies conducted

  • Comparative studies using Keytruda (anti-PD-1) to measure tumor lysis
  • Comparative studies using Yervoy (anti-CTLA4)
  • Effect of drug candidate(s) on TIL 2265 migration in 3D co-cultures towards Tumor 2265
  • Characterization of immune sub-populations present in TIL 2265 in response to drug treatment

For additional information and data related to these cell lines, please Contact us to learn more