LAG3 and cancer: Although TH1-polarization within the tumor cell nests, especially in HPV-positive cancers (Figure 2), suggests the potential involvement of T-cell immunity in response to tumor-specific antigens, our data simultaneously indicates that TH1-polarized helper T cells could be dysfunctional in view of high expression of PD-1 (Figure 3), which can serve as one of T cell exhaustion markers such as Eomes, TIM-3, LAG-3, etc (46).