Recent clinical studies have found that there are still a large number of patients who do not respond to immune checkpoint inhibitors (ICIs). Improving immunotherapy response in ccRCC patients is an urgent clinical need. Targeting different components of the tumor immune microenvironment becomes a breakthrough point for overcoming the immunotherapy resistance and optimizing therapeutic strategies in advanced ccRCC. Several novel immunotherapeutic strategies are currently under clinical investigation, including targeting other co-inhibitory and co-stimulatory molecules, modified cytokine therapies, small-molecule immunomodulators, targeting immune metabolism, and cancer vaccines, each of which target different immunomodulatory pathways in the tumor immune microenvironment for the treatment of ccRCC. In this paper, we provide an overview of the current challenges faced by immunotherapy for advanced ccRCC and review novel immunotherapy strategies based on the tumor immune microenvironment.

Objective To investigate the feasibility and safety of transvaginal endoscopic cholecystectomy.Methods The clinical data of 88 female patients who underwent cholecystectomy at the Qilu Hospital of Shandong University from May to November, 2009 were retrospectively analysed. Among all the patients, 32 received transvaginal endoscopic cholecystectomy ( NOTES group) and the remaining 56 patients received laparoscopic cholecystectomy (LC). Thirty-two patients who received LC at the same period were selected (LC group)acccording to age, body mass index, type and severity of disease to conduct a matched case-control study. The differences in time span of postoperative pain, anodyne dose, enterokinesia recovery time, operation time, out-ofbed activity time, average hospital stay and hospitalization expenses between the two groups were compared using the paired t test. Results Cholecystectomies were successfully carried out for all the patients. The intraoperative blood loss, operation time, degree of pain, anodyne doses, enterokinesia recovery time, out-of-bed activity time,average hospital stay and hospitalization expenses were (5.7 ± 1.5 ) ml, ( 76 ± 27 ) minutes, 2.2 ± 0.6, ( 10 ±6) mg, (25±5) hours, (9±3) hours, (2.1 ±1.2) days and (1.12±0.34) ×104 yuan in NOTES group, and they were ( 13.9 ± 3.1 ) ml, (38 ± 16) minutes, 6.7 ± 1.5, (28 ± 8) mg, (45 ± 8) hours, (26 ± 6) hours,(4.3 ± 2.1 ) days and ( 1.54 ± 0.18 ) × 104 yuan in the LC group. There were significant differences between the two groups (t = 5.098, - 4.712, 2.417, 3.203, 3.089, 4.136, 4.786, 3.917, P ＜ 0.05 ). Conclusion Transvaginal endoscopic cholecystectomy is safe and feasible, and it is superior to tranditional LC.

Objective:To investigate the feasibility and safety of a new method of natural orifice transluminal endoscopic surgery(NOTES) -totally transtracheal endoscopic thyroidectomy(TTET) .Methods:Three miniature swines and 6 beagle dogs were underwent TTET.Under general anesthesia,special designed endotracheal tube with 2-channel was used and endoscope and instruments were inserted through the respective channel.Incision of tracheal anterior wall was accomplished and partial or subtotal thyroidectomy was performed.Finally,the defects in the trachea were sutured with ENDO STITCH instrument.Results:Partial thyroidectomy was successfully accomplished on 3 pigs and subtotal thyroidectomy was done on 6 dogs.No serious complications such as anoxia,asphyxia,airway obstruction and death occurred during the operation.Animals were sacrificed 2h after the procedure and incision of trachea was found to be closely sutured.There were no subcutaneous emphysema and haematoma formation.Conclusion:Preliminary experimental results showed the feasibility and safety of TTET.Transtracheal access maintains the integrity of cervical tissues and achieves an optimal cosmetic outcome.TTET may open up a new field of NOTES on thyroid surgery.