Hello Ananya,

The reason is as follows.

High T cell densities may mediate effective killing. High T cell densities enable high contact frequencies and multiple T cell–tumor cell encounters. This may increase the likelihood of multiple T cell simultaneously attacking a single target cell (cancer cell). In addition, cytotoxic cytokine release, including interferon-γ and tumor necrosis factor, is positively associated with high density T cell infiltration.

High T cell density which can be called swarming enables efficient apoptosis induction by favoring serial perforin-dependent hits, preferentially by different T cells whereas the ineffective killing at low T cell density largely relies upon single encounters.

A successful T cell effector function correlates with high local T cell densities. If a 1:1 ratio for T cell : cancer cell is taken, the T cells will form predominantly short-lived interactions with target cells (cancer cells) which rarely result in direct apoptosis induction.

The individually ineffective T cell contacts induce sublethal damage, which becomes integrated over time in the target cell until apoptosis is induced. Through such a multi-hit mechanism, T cell induce tumor cell death when density is high, whereas tumor cells repair sublethal damage and survive when T cell density is low. This mechanism of “additive cytotoxicity” explains how individually ineffective interactions become effective at high T cell density.

Thus, in apoptosis assay, the T cells have to be higher in density than the target cells ( cancer cells).

Best.

Malcolm Nobre thank you for your answer madam. I would like to add some points regarding my question. In literature it is written that upon interaction between PD-1 and PDL1; cancer cell causes apoptosis of T cell (jurkat or human T cell). To check the apoptosis of T cell, most of then perform apoptosis assay by taking T cell : cancer cell ratio= 5:1. Can you tell me why this particular ratio is taken in that context?