Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors

Figures & data

Figure 1. Schema for treatment on the three arms of the study.

Table 1. Demographics and baseline characteristics of patients (N = 33).

Variable	HT + ACT (n = 10)	HT + ACT + anti-PD-1 (n = 11)	HT + ACT + CT (n = 12)	p Value
Sex				0.837
Male	4	5	4
Female	6	6	8
Age				0.698
≥65	3	2	4
<65	7	9	8
ECOG-PS				0.951
0	3	3	4
1	7	8	8
TNM stages				0.742
III	4	3	5
IV	6	8	7
Tumor types				0.478
Ovarian cancer	3	0	3
Pancreatic cancer	1	1	0
Gastric cancer	2	1	1
Colorectal cancer	0	4	3
Cervical cancer	1	2	1
Endometrial cancer	1	2	2
Peritoneal cancer	1	1	1
Malignant mesothelioma	1	0	1
Previously treatment				0.943
Surgery	5	6	8
Chemotherapy	7	7	8
Radiation therapy	3	3	2
Disease control				0.579
CR	0	1	2
PR	3	2	2
SD	4	3	5
PD	3	5	3
Objective response rate (RR)	30.00%	27.30%	30.00%
Disease control rate (DCR)	70%	55%	75%

Table 2. Clinical responders and non-responders distribution among enrolled patients.

Tumor types	Number of patients	Clinical response				Number (%) of patients
		CR	PR	SD	PD	ORR (%)	DCR (%)
Ovarian cancer	6	1	2	2	1	50.00	83.30
Pancreatic cancer	2	0	0	1	1	0.00	50.00
Gastric cancer	4	0	1	2	1	25.00	75.00
Colorectal cancer	7	2	1	2	2	42.80	74.30
Cervical cancer	4	0	1	2	1	25.00	75.00
Endometrial cancer	5	0	1	2	2	20.00	60.00
Others	5	0	1	1	3	20.00	40.00
All	33	3	7	12	11	30.30	66.70

CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: objective response rate (i.e., CR and PR); DCR: disease control rate (i.e., CR, PR, and SD).

Figure 2. Serum cytokines secretion were detected and compared by paired t test in different groups. Comparison of IL-2 (A), IL-4 (B), TNF-α (C) IFN-γ (D) IL-6 (E), and IL-10 (F) levels were performed pre and post treatment in different groups of patients according to clinical response.

Figure 3. TCR diversity were compared in different group by paired t test. (A, B) Alterations of Shannon index and clonality in all patients; (C, D) Shannon index and clonality significantly changed in tumor remission group, while Shannon index and clonality did not significantly change in Non remission group; (E, F) Unique TCR subclones increased and the shared TCR subclones decreased in patients with tumor remission; (G, H) The unique and the shared TCR subclones had no significant changes in patients of non-remission group.

Figure 4. Peripheral blood T cell phenotype measurements via cytometry before and after the treatment. CD8+/CD28+ (E) T cell subset was significantly increased after the combined treatment (p < 0.05); CD4+/CD25+/CD127+ (D) cell subset was significantly decreased after the combined treatment (p < 0.05); CD3+ (A), CD3+/CD4+ (B), and CD3+/CD8+ (C) and CD8+/CD28− (F) cell subsets were not significantly changed after the combined treatment (p > 0.05).

Table 3. Summary of hematological and treatment-associated adverse events.

	HT + ACT (n = 10)		HT + ACT + anti-PD-1 (n = 11)		HT + ACT + CT (n = 12)
	All grades, n (%)	Grade 3 or 4, n (%)	All grades, n (%)	Grade 3 or 4, n (%)	All grades, n (%)	Grade 3 or 4, n (%)
Leucopenia	0	0	0	0	2 (16.7%)	0
Neutropenia	0	0	0	0	1 (8.3%)	0
Anemia	0	0	2	0	2 (16.7%)	1 (8.3%)
Thrombocytopenia	0	0	0	0	1 (8.3%)	0
Skin rash	1 (10%)	0	2 (18.2%)	0	1 (8.3%)	0
Hand–foot syndrome	0	0	0	0	2 (16.7%)	0
Pigmentation	0	0	1 (9.1%)	0	1 (8.3%)	0
Blistering	1 (10%)	0	1 (9.1%)	0	1 (8.3%)	0
Subcutaneous fat induration	1 (10%)	0	2 (18.2%)	1 (9.1%)	1 (8.3%)	0
Local heating pain	1 (10%)	0	1 (9.1%)	0	1 (8.3%)	0
Nausea	2 (20%)	0	0	0	1 (8.3%)	0
Vomiting	1 (10%)	0	1 (9.1%)	0	2 (16.7%)	0
Diarrhea	1 (10%)	0	2 (18.2%)	0	1 (8.3%)	0
Fatigue	2 (20%)	0	2 (18.2%)	0	3 (17.6%)	0
Abdominal pain	1 (10%)	0	0	0	1 (8.3%)	0
Sinus tachycardia	0	0	0	0	1 (8.3%)	0
ALT elevation	0	0	0	0	1 (8.3%)	0
AST elevation	0	0	0	0	0	0
Increased creatinine	0	0	0	0	0	0
Hyponatraemia	0	0	0	0	0	0
Hypoalbuminemia	0	0	0	0	0	0

There was no occurrence of treatment related deaths in all groups. Severity was graded according to National Cancer Institute Common Toxicity Criteria, version 4.0.