Patient characteristics

The patients’ average age was 57.7 ± 9.6 (range: 29–72) years, most of whom were male (89.3%, 125/140). Among these patients, hepatitis B virus infection was the main cause of liver disease (93.6%, 131/140), and most had cirrhosis (93.6%, 131/140). The number of patients in the T, T + A, and T + A + C groups were 20 (14.3%), 66 (47.1%), and 54 (38.6%), respectively. The average positive expression rates of TIGIT on T cells in the T, T + A, and T + A + C groups were 11.64%, 11.57%, and 12.60%, respectively. Table 1 shows the patients’ detailed baseline demographic data.

Table 1 Baseline demographic data of patientsRelationship between TIGIT expression on T cells and the patients’ clinical and immune characteristics

The patients were divided into high- and low-expression groups based on the median positive expression rate (10.44%) of TIGIT in T cells (Table 2). Patients with a higher TIGIT expression in T cells had larger and more late-stage tumors, a higher proportion of regulatory and helper T/suppressor T cells, higher plasma IL-6 and IL-10 concentrations, and lower IFN-γ concentrations (Table 3).

Table 2 Correlation between TIGIT expression on T cells and the clinical characteristics of patients TIGIT: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domainsTable 3 Correlation between TIGIT expression on T cells and patient immune indicators TIGIT: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domainsTIGIT expression and prognosis in patients in the T group

Of the 20 patients who received TACE treatment alone, no significant change was observed in the proportion of TIGIT + T cells three days after treatment compared to baseline (P = 0.325) (Fig. 1a and b). In addition, plasma CD155 expression was significantly lower at three days after treatment than before treatment (P = 0.032).

Fig. 1

A, Changes in the proportion of TIGIT + T cells before and after TACE treatment. B, Changes in CD155 expression in the plasma before and after TACE treatment. C, PFS rates of patients in the TIGIT high- and low-expression groups who received TACE treatment alone. D, PFS rates in patients with increased and decreased TIGIT expression after TACE treatment

TACE: transcatheter arterial chemoembolization; TIGIT: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains; PFS: progression-free survival

According to the median positive expression rate (11.60%) of TIGIT in T cells of patients receiving TACE treatment alone, the patients were divided into high- and low-expression groups. No significant difference was observed in PFS time between the two groups (TIGIT low: median PFS time, 10.5 months; 95% confidence interval [CI], 8.331–12.669 and TIGIT high: median PFS time, 8.9 months; 95% CI, 6.576–11.224; P = 0.386) (Fig. 1c).

According to the changes in TIGIT expression after TACE treatment, patients were divided into TIGIT elevation and TIGIT reduction groups (Fig. 1d). The PFS time of patients in the TIGIT elevation group was significantly longer than that of those in the TIGIT reduction group (TIGIT elevation: median PFS time, 12.9 months; 95% CI, 9.394–16.406 and TIGIT reduction: median PFS time, 9.2 months; 95% CI, 8.679–9.721; P = 0.013).

TIGIT expression and prognosis in patients in the T + A and T + A + C groups

Patients were divided into high- and low-expression groups based on the median positive expression rate of TIGIT in T cells of patients receiving TACE combined with either apatinib and or apatinib and camrelizumab treatment. No significant differences were observed in PFS (TIGIT low: median PFS time, 8.5 months; 95% CI, 7.656–9.344 and TIGIT high: median PFS time, 9.1 months; 95% CI, 6.849–11.351; P = 0.359) and OS (TIGIT low: median OS time, 18.4 months; 95% CI, 15.586–21.214 and TIGIT high: median OS time, 19.1 months; 95% CI, 16.943–21.257; P = 0.123) between the high and low TIGIT expression groups in patients treated with TACE combined with apatinib (Fig. 2a and b).

Fig. 2

A, PFS rates of patients in the TIGIT high- and low-expression groups who received TACE combined with apatinib treatment. B, OS rates of patients in the TIGIT high- and low-expression groups who received TACE combined with apatinib treatment. C, PFS rates of patients in the TIGIT high- and low-expression groups who received TACE combined with apatinib and camrelizumab treatment. D, OS rates of patients in the TIGIT high- and low-expression groups who received TACE combined with apatinib and camrelizumab treatment

TACE: transcatheter arterial chemoembolization; TIGIT: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains; PFS: progression-free survival; OS: overall survival

In patients treated with TACE combined with apatinib and camrelizumab, the PFS time of patients in the low TIGIT expression group was significantly longer than that of those in the high TIGIT expression group (TIGIT low: median PFS time, 11.3 months; 95% CI, 8.756–13.844 and TIGIT high: median PFS time, 7.4 months; 95% CI, 4.636–10.064; P < 0.001). The OS time of patients in the low TIGIT expression group was significantly longer than that of those in the high TIGIT expression group (TIGIT low: median OS time, 24.9 months; 95% CI, 16.588–33.212 and TIGIT high: median OS time, 20.2 months; 95% CI, 15.790–24.610; P = 0.016) (Fig. 2c and d).

Comparison of survival prognosis between the T + A + C and T + A groups

As shown in Fig. 3a and b, patients in the T + A + C group had significantly longer PFS (T + A + C: median PFS time, 9.4 months; 95% CI, 7.171–11.729 and T + A: median PFS time, 8.5 months; 95% CI, 7.438–9.562; P = 0.032) and OS times (T + A + C: median OS time, 22.1 months; 95% CI, 20.180–24.020 and T + A: median OS time, 18.4 months; 95% CI, 16.365–20.435; P = 0.040) than those in the T + A group.

Fig. 3

A, PFS survival rates of patients receiving TACE combined with apatinib and camrelizumab and TACE combined with apatinib treatment. B, OS rates of patients receiving TACE combined with apatinib and camrelizumab or TACE combined with apatinib treatment. C, PFS rates in TIGIT low expression patients receiving TACE combined with apatinib and camrelizumab treatment and in patients receiving TACE combined with apatinib treatment. D, OS rates in TIGIT low expression patients receiving TACE combined with apatinib and camrelizumab treatment and in patients receiving TACE combined with apatinib treatment. E, PFS rates in TIGIT high expression patients receiving TACE combined with apatinib and camrelizumab treatment and in patients receiving TACE combined with apatinib treatment. F, OS rates in TIGIT high expression patients receiving TACE combined with apatinib and camrelizumab treatment and in patients receiving TACE combined with apatinib treatment

TACE: transcatheter arterial chemoembolization; TIGIT: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains; PFS: progression-free survival; OS: overall survival

Considering the significant differences in survival between high- and low-expression TIGIT groups receiving TACE combined with apatinib and camrelizumab, we analyzed the survival prognosis of patients with high and low TIGIT expression in the T + A + C group and all patients in the T + A group, respectively. The results are shown in Fig. 3c and d. Compared with patients in the T + A group, those in the TIGIT low-expression group who received TACE combined with apatinib and camrelizumab had longer PFS (T + A + C-TIGIT-low: median PFS time, 11.3 months; 95% CI, 8.756–13.844 and T + A: median PFS time, 8.5 months; 95% CI, 7.438–9.562; P < 0.001) and OS times (T + A + C-TIGIT-low: median OS time, 24.9 months; 95% CI, 16.588–33.212 and T + A: median OS time, 18.4 months; 95% CI, 16.365–20.435; P = 0.004). As shown in Fig. 3e and f, compared with patients in the T + A group, those in the TIGIT high-expression group who received TACE combined with apatinib and camrelizumab had shorter PFS (T + A + C-TIGIT-high: median PFS time, 7.4 months; 95% CI, 4.636–10.064 and T + A: median PFS time, 8.5 months; 95% CI, 7.438–9.562; P = 0.041). However, no significant difference existed in OS time between the two groups (T + A + C-TIGIT-high: median OS time, 20.2 months; 95% CI, 15.790–24.610 and T + A: median OS time, 18.4 months; 95% CI, 16.365–20.435; P = 0.984).