VC TILs may have higher stem-like property than CC TILs
A recent study found that tumor-infiltrating CD8+ T cells can be divided
into two functionally distinct subgroups: a terminally differentiated
group marked by high expression of immune-checkpoint molecules such as
PD-1 and TIM-3, and a stem-like group with low checkpoints but high TCF1
and CD28 expression(19). PD-1 (programmed death receptor 1, also known
as CD279) is a co-inhibitory receptor restraining T cell function and
anti-tumor response, thus considered as a marker of T cell
exhaustion(20). TCF1 is a key transcription factor in stem cell-like T
cells, and it plays a critical role in sustaining immune response to
tumor and chronic virus infection(21, 22). To better characterize the
functional profile of TILs after the REP process, we analyzed the
expression of PD-1 and TCF1 in VC and CC TILs. The percentage of PD-1
positive CD4+ and CD8+ T cells in CC TILs is only around 10%, but it is
even lower in VC TILs (Figure 4A). Almost 100% of CD8+ VC TILs is
TCF1+, which is significantly higher than that in CC TILs (Figure 4B),
indicating that VC TILs may possess a
stronger stem-like property and, thus, a better potential to amplify and
survive in vivo than CC TILs. We further examined the memory phenotype
of VC and CC TILs by CD45RA and CCR7 staining and found that VC TILs
have a higher percentage of naïve and central memory T cells (Tcm)
(Figure 4C) and a lower percentage of effector memory and effector
memory RA T cells (Tem and TemRA) (Figure 4D) than CC TILs, especially
in CD4+ T cells, which is consistent with the higher stem-like phenotype
of VC TILs.
In addition, we profiled our TIL samples by CD103 and CD39 staining as
CD103+CD39+ tumor-infiltrating CD8+ T cells that may represent
tumor-reactive cells in solid tumors and are associated with better
overall survival(23). We observed that 6/10 of CC TIL samples and 2/4 of
VC TIL samples have more than 20% CD8+ T cells showing CD103 and CD39
double positivity, but this ratio is low in CD4+ T cells (Figure 4E).