ObjectivesTo evaluate the nature, diagnosis, treatment and prognosis of second primary renal cell carcinoma (SPRCC).Materials and MethodsWe retrospectively collected data from 118 patients with SPRCC. Clinical characteristics, imaging features and treatments were analyzed and comparisons between SPRCC and renal metastases (RM) were made.ResultsSPRCC accounts for 11.4% of all RCC. The most common types of extrarenal malignancies included lung, colorectal, breast and gynecological cancers. The median age was 58.5 years old, and 61.0% (72/118) of the patients were male. About 5.1% of the patients presented with symptoms. The average tumor diameter was 4.4 cm (1-8.4 cm). The diagnostic specificity of enhanced computed tomography (CT) was 80.1%. When comparing with RM, more patients with stage I–II extrarenal malignancy and less patients with bilateral, multiple, and endogenic renal masses on computed tomography were found in the SPRCC group. A total of 110 SPRCC patients underwent surgery, including 48 radical nephrectomies and 62 partial nephrectomies. The median overall survival time was 117 months. Female, asymptomatic status, no distant metastasis, and surgical treatment predicted a better survival.ConclusionsSPRCC are not uncommon, and it should be considered during the follow-up of patients with nonrenal malignancy. The differential diagnosis between SPRCC and RM was mainly based on imaging and puncture biopsy.

Objective Second primary renal cell carcinoma (2nd RCC) refers to renal cell carcinoma (RCC) diagnosed after another unrelated malignancy. This study aims to compare the clinical manifestation, pathology, treatment, and prognostic features of patients with 2nd RCC and first primary renal cell carcinoma (1st RCC). Materials and methods Data of the patients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. Results The most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than in those of 1st RCC patients. For 2nd RCC patients, fewer had clinical symptoms and renal masses tend to be smaller. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent a partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs were commonly identified in the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. Conclusions Second RCC is not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately.

Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) blockade are standard of care for many patients with advanced or metastatic cancer. However, a majority of patients remain resistant to these treatments. It has been reported that local oncolytic viral infection of tumors is capable of overcoming systemic resistance to PD-1 blockade, and strongly suggest the combination therapy of virotherapy with PD-1 blockade to improve therapeutic efficacy in tumors that are refractory to checkpoint blockade. We investigate the antitumor effects of an E1B55KD deleted oncolytic adenovirus H101, in combination with a humanized anti-PD-1 monoclonal antibody Camrelizumab on cancer. Combination of H101 with Camrelizumab demonstrated more potent antitumor effects than monotherapy in immune system humanized NSG mice subcutaneous (S.C.) tumor model. Increased tumor infiltrating T cells including the total and IFN-γ-expressing CD8+ T cells in the combination treatment group were observed. H101 infection induced decreased expression of CD47 on cancer cells, thereby promoting macrophage to phagocytose cancer cells. With the activation of macrophage by H101, increased levels of cytokines including TNF, IL-12 and IFN-γ were observed when induced THP-1 cells were co-cultured with H101-treated cancer cells, which further induced increased expressions of IFN-γ in T cells. Eliminating the IL-12 by anti-IL-12 neutralizing antibodies abolished IFN-γ production from T cells, showing activation of macrophages by H101 induced oncolysis to promote IFN-γ secretion of T cells via IL-12. Meanwhile, infection with H101 induced upregulation of PD-L1 on YTS-1 cells. These results suggested that H101 works synergistically to enhance therapeutic efficacy of PD-1 blockade on cancer by suppressing CD47 signaling, which may promote phagocytose of macrophages to tumor cells and activate CD8+ T cells. Combination of H101 with PD-1 blockade would be a novel strategy for treating cancer.