Table 1.
Patient characteristics and treatments in TIM-3 expression change groups
| Clinical parameter | TIM-3 decrease (n=9) | TIM-3 increase (n=6) | Total (N=15) | Significance* (decr. vs incr.) | |
| Baseline/treatment characteristic | Patients, n (% of total) | P value | |||
| Gender | Female | 7 (77.8) | 4 (66.7) | 11 (73.3) | ns |
| Male | 2 (22.2) | 2 (33.3) | 4 (26.7) | ns | |
| Age group | Adult (25–65 years) | 6 (66.7) | 4 (66.7) | 10 (66.7) | ns |
| Elderly (>65 years) | 3 (33.3) | 2 (33.3) | 5 (33.3) | ns | |
| WHO perf. status (0–5) | 0 | 1 (11.1) | 0 (0.0) | 1 (6.7) | ns |
| 1 | 4 (44.4) | 2 (33.3) | 6 (40.0) | ns | |
| 2 | 4 (44.4) | 3 (50.0) | 7 (46.7) | ns | |
| 3 | 0 (0.0) | 1 (16.7) | 1 (6.7) | ns | |
| Tumor type | Pancreatic | 1 (11.1) | 1 (16.7) | 2 (13.3) | ns |
| Colorectal | 1 (11.1) | 1 (16.7) | 2 (13.3) | ns | |
| Prostate | 1 (11.1) | 0 (0.0) | 1 (6.7) | ns | |
| Mesothelioma | 0 (0.0) | 1 (16.7) | 1 (6.7) | ns | |
| Melanoma | 1 (11.1) | 0 (0.0) | 1 (6.7) | ns | |
| Lung (NSCLC) | 1 (11.1) | 0 (0.0) | 1 (6.7) | ns | |
| Cervical | 1 (11.1) | 0 (0.0) | 1 (6.7) | ns | |
| Ovarian | 2 (22.2) | 2 (33.3) | 4 (26.7) | ns | |
| Breast | 1 (11.1) | 1 (16.7) | 2 (13.3) | ns | |
| Sample material | Biopsy | 7 (77.8) | 3 (50.0) | 10 (66.7) | ns |
| Ascites | 1 (11.1) | 2 (33.3) | 3 (20.0) | ns | |
| Pleural | 1 (11.1) | 1 (16.7) | 2 (13.3) | ns | |
| Oncolytic virus arming | GMCSF | 6 (66.7) | 4 (66.7) | 10 (66.7) | ns |
| CD40L | 1 (11.1) | 2 (33.3) | 3 (20.0) | ns | |
| No transgene | 2 (22.2) | 0 (0.0) | 2 (13.3) | ns | |
| Virus sensitizer† | Cyclophosphamide | 8 (88.9) | 5 (83.3) | 13 (86.7) | ns |
| Temozolomide+CP | 1 (11.1) | 1 (16.7) | 2 (13.3) | ns | |
*Patients were stratified into TIM-3 decr. and TIM-3 incr. groups based on direction of TIM-3 expression change: Fisher’s exact test was used for categorical variables between TIM-3 groups, while unpaired t-test was also tested for the linear variable age.
†Virus sensitizers include low-dose chemotherapy regimens routinely used in an adjuvant setting with oncolytic viruses: Low-dose cyclophosphamide (CP) was used for selective reduction of regulatory T cells.21 CP was administered either metronomically orally, starting 1 week before virus injection and continued until progression, or intravenously on the day of virus treatment, or as a combination of these. Low-dose pulse of temozolomide was administered concurrently orally (1 week before, 1–2 weeks after the virus treatment, or as a combination of these) to induce immunogenic cell death, as reported.21
CD40L, CD40 ligand; CP, cyclophosphamide; decr., drecease; GMCSF, granulocyte-macrophage colony-stimulating factor; incr., increase; ns, not significant; NSCLC, non-small cell lung carcinoma; TIM-3, T-cell immunoglobulin and mucin domain-3.