Figure 2.

Intratumoral balance of anti- vs pro-tumorigenic CD4⁺ T_H cells determine immune response outcome. Activation and downregulation of specific T_H cells modulate intratumoral balance of stimulatory and suppressive effectors and modulates tumor response to immunotherapy. Polarization and activation of T_H1, T_H9 and T_fh subtypes induce secretion of proinflammatory cytokines, and, coupled with simultaneously diminished activity of immunosuppressive T_H2 and T_reg cells, tip the balance towards anti-tumor immune response and induce tumor regression (left). On the contrary, heightened activity of the immunosuppressive populations and secretion of inhibitory cytokines, and concurrent downregulation of immunostimulatory T_H1, T_H9 and T_fh cells induce a protumorigenic microenvironment, resulting in disease progression (right). To shift the balance to either end of the equilibrium, a concerted effort by multiple T_H subtypes are necessary and may not be achieved by alteration in the functional state of a single T_H subtype.