2.1T cells affect prognosis and efficacy of immunotherapy in
NSCLC patients
The number of circulating lymphocytes, including the proportion of and
the absolute number of lymphocytes, is an important indicator of the
efficacy of the body’s immune function and the degree of stress[77]. Interaction and influence each other exist
between the various cells in the immune system,the appropriate ratio
for immune cells in the body is an important guarantee for their
function. Peterson et al explored the prognostic relevance of Treg cells
in 64 patients with stage INSCLC and found that a higher proportion of
Treg cells in the tumor significantly increased the risk of recurrence.
Immunohistochemistry has detected Treg cells in 51% of NSCLC patients.
Therefore, Treg cells can be identified as an important risk factor for
postoperative recurrence of NSCLC [78]. In
addition, Liu et al reported that a high Foxp3+Treg/CD8+ T cell ratio predicted poor response to
platinum-based chemotherapy in advanced NSCLC. Given this apparent
functional relevance of Treg cells in NSCLC, targeting Treg cells might
be an interesting approach for immunotherapy of lung cancer[79].
Clinically, the absolute number of lymphocytes is much more important
than the proportion. Tumors can significantly inhibit the proliferation
of bone marrow cells during the developmental period, significantly
decreasing the absolute number of various immune cells, including
lymphocytes [80-81]. At the same time, one of the
main consequences of chemotherapy and radiotherapy is damaging the bone
marrow[82]. As a result, it decreases the absolute
number of lymphocytes that is closely related to the prognosis and
efficacy of immunotherapy[83-84]. Numerous studies
have shown that low lymphocyte absolute count (ALC) is an independent
negative prognostic factor for advanced malignant tumors[85]. Oh et al found that the baseline absolute
lymphocyte count level is an independent prognostic factor of rectal
adenocarcinoma patients receiving preoperative radiotherapy and
chemotherapy in different treatment periods and follow-up periods. In
one study, the absolute lymphocyte count decreased after preoperative
radiotherapy and chemotherapy, reaching the lowest level at 1 month but
gradually increased after the end of radiotherapy and chemotherapy[86]. Furthermore, Xia Ying et al. found that the
absolute numbers but not the relative numbers of lymphocyte subsets
CD3+, CD4+, CD8+,
B, and NK cells were significantly damaged in NSCLC patients,and were
closely related to the disease progression and progression-free survival
period. And they were served as biomarkers for disease prognosis and
efficacy. The work indicated that only paying attention to the
proportion of lymphocyte subsets in clinic is easy to lead to clinical
misjudgment [87].
T cells can also effectively reduce NSCLC by increasing their activity.
IFN- γ promotes the activity of T cells by inducing the presentation of
antigen-presenting cells (APCs) and upregulating the expression of MHC I
/ peptide complex on APCs to reactivate and induce the proliferation of
antigen-specific CD8+ T cells. The activated tumor
antigen-specific CD8+ T cells can recognize and
secrete cytotoxic molecules to kill tumor
cells[88]. Wu et al showed that Fuzheng anticancer
formula effectively enhances the secretion of IFN- γ by
CD8+ T cells, which is critical in clearing tumor
cells[89] . CTLA-4 and PD-L/PD-lL are the most
studied checkpoint pathways, and they inhibit T cell activity in
different ways[90-91] . CTLA-4 regulates T cell
proliferation early in immune response[92] ,
whereas PD-1 suppresses T cells later in immune
response[93] . The immune checkpoint inhibitors
including ipilimumab and tremelimumab (CTLA-4 monoclonal antibody),
nivolumab and pembrolizumab (PD-1 monoclonal antibody), atezolizumab and
durvalumab (PD-L1 monoclonal antibody) have opened a new era in the
treatment of advanced NSCLC. Nivolumab and pembrolizumab have been
approved by FDA and EMA for the second-line treatment of
NSCLC[94-95] .