Evaluation of Immuno-oncology Treatments with Histopathology

Immuno-oncology involves leveraging the power of the immune system to detect and eliminate cancer cells. Oncologists are increasingly turning their attention to immune-oncology, since it offers a novel way to improve patient outcomes. It has been recognized that the infiltration of tumors by innate and adaptive immune cells is associated with improved clinical outcomes and responses to treatments, and immuno-oncology seeks to harness and direct this effect to patients’ benefit. Knowledge of the mechanisms involved in how cancers escape from immune attack has advanced considerably in recent years. Targeting of processes utilized by tumor cells to effect immune checkpoint receptors and ligands, such as PD-L1, and the modulation of tumor antigen presentation is the basis of immuno-oncology treatments.

At Visikol, we have developed numerous techniques for quantitatively evaluating the infiltration of immune cells, especially T cells, into tumors utilizing histopathological techniques combined with advanced image processing. Using immunohistochemical techniques, immune cells can be labeled and the degree of infiltration into a tumor can be quantitively assessed.

The majority of tumor infiltrating cells were CD45+ and CD3+ cells, which totaled ~4.5% of the tumor cells, with PD-1+ cells being ~1.5% of the total tumor cells (Figure 1). Analysis of the distribution of the distances of each cell from the edge of the tumor (as defined by PanCK+ regions) was conducted. The distance between each cell within the tumor region and the edge of the tumor region was measured (Figure 2 depicts this analysis). As can be seen, a majority or near majority of cell subtypes were found within 10 microns of the edge of the tumor spheroid.  The surveyed cell types showed fairly similar distribution patterns within the tumor (Figure 4).

Figure 1. Fluorescent microscopic image of immunohistochemical staining of tumor section. Blue: DAPI labeling nuclei; Green: CD3 labeling T cells; Red: CD45 labeling T cells

Figure 2. Analysis of distance of T cells from tumor boundary in fluorescent microscopy histopathology image

Figure 3. Violin plot distribution of distance into tumor various T cell populations have penetrated

Figure 4. Isodensity plot illustrating relative distribution of CD3+ T cells within tumor tissue

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