Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
© 2024. The Author(s).

We sought to investigate the efficacy of adoptive transfer of TILs plus anti-PD1 therapy in metastatic osteosarcoma patients.
A total of 30 patients received anti-PD1 therapy (Group 1) while 30 patients were subjected to TILs plus anti-PD1 therapy (Group 2). Progression-free survival time (PFS) and overall survival time (OS) were analyzed using Kaplan-Meier analysis. Potential prognostic factors were analyzed using univariate and multivariate analyses.
The ORR in Group 2 is 33.3%, which is significantly higher than Group1 (6.67%). In addition, we found significantly prolonged mPFS (5.4 months) and mOS (15.2 months) in Group 2 compared to those in Group 1, which recorded mPFS and mOS of 3.8 and 6.6 months, respectively. Univariate and multivariate analyses indicate that patients with more infusions of TIL numbers and CD8+TILs or less infusions of CD8+ PD1+TILs and CD4+FoxP3+ TILs show increased PFS and OS. Moreover, PD1hi is another good prognostic factor that predict PFS and OS.
Overall, these findings indicated that TILs plus anti-PD1 therapy has significant clinical outcomes in metastatic osteosarcoma patients. However, further studies are essential to validate and characterize the therapeutic activity of TILs plus anti-PD1.
© 2020 The Authors.

The pathological subtype of osteosarcoma is one of the most common malignant bone tumors. Notably, chemotherapy-resistant metastatic osteosarcoma has been reported to cause significant mortality and shows poor prognosis with the currently available multidisciplinary treatments. This study investigated whether combined adoptive TIL and anti-PD1 therapy improves the prognosis of patients with chemotherapy-resistant metastatic osteosarcoma.
A total of 60 patients with chemotherapy-resistant metastatic osteosarcoma between June 2016 and March 2018 were enrolled. The primary endpoint was to evaluate the safety and adverse effects (AEs) of infusions of TIL and anti-PD1 therapy in the patients. Besides, secondary endpoints included assessing the objective response rate (ORR), progression-free survival time (PFS), and overall survival time (OS).
We reported that combined TIL therapy and anti-PD1 therapy is safe and all treatment-related AEs were reversible or manageable. The ORR of all the patients is 36.67%, and patients with more infusions of TIL and CD8+TIL, less infusions of CD8+PD1+TIL, and less infusion of CD4+FoxP3+TIL exhibited increased PFS and OS.
This study determined that combined TIL and anti-PD1 therapy is safe and effective in metastatic osteosarcoma patients with chemotherapy resistance.
Copyright © 2020 Xiang Zhou et al.

We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative.
A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients.
The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy.
Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.
Copyright © 2020 Huanhuan Yin et al.