Intratumoral lymphocyte density

Tumor infiltrating lymphocytes (TILs) are immune cells — primarily T cells and B cells — that have migrated from the bloodstream into the tumor tissue. Their presence indicates that the immune system has recognized the tumor and is mounting a response. TIL density is one of the strongest prognostic biomarkers across multiple cancer types.

In clinical practice, TILs are scored visually on H&E-stained slides, typically as a percentage of the stromal area occupied by lymphocytes. The International TILs Working Group classifies TIL levels as: absent (no lymphocytes), non-brisk (focal or patchy lymphocytic infiltrate), and brisk (dense, diffuse lymphocytic infiltrate throughout the tumor). Brisk TIL infiltration is associated with better prognosis in breast cancer, melanoma, and colorectal cancer.

An important distinction is where the lymphocytes are located. Intratumoral TILs are lymphocytes that have penetrated into the tumor epithelium itself — they are in direct contact with cancer cells. Stromal TILs are found in the surrounding stroma but have not crossed into the tumor nests. HistoAtlas measures both compartments separately: intratumoral lymphocyte density (this feature) and stromal lymphocyte density.

HistoAtlas measures intratumoral lymphocyte density as cells per mm² — a continuous, quantitative measurement computed by deep learning cell detection across the entire tumor area. This overcomes the limitations of traditional categorical scoring (absent/non-brisk/brisk), which suffers from inter-observer variability and loses granular information. The formula is:

$$\text{Density} = \frac{N_{\text{lymph}}^{\text{IT}}}{A(\Omega_{\text{Tumor}})}$$

where $N_{\text{lymph}}^{\text{IT}}$ is the count of lymphocytes within the tumor epithelium and $A(\Omega_{\text{Tumor}})$ is the tumor area in mm².