Agonistic anti-CD40 antibody therapy is effective against postoperative cancer recurrence and metastasis in a murine tumor model.

Postresection recurrences of cancer arising from occult tumor deposits, either local or metastatic, represent major causes of death in patients with operable solid tumors. Thus, new therapies are required that complement existing treatments to eradicate these occult deposits. Agonistic anti-CD40 antibody is one of the most powerful new cancer immunotherapies, enhancing immune priming of effector CD8 T cells by dendritic cells, leading to increased antitumor activity. We investigated the use of anti-CD40 antibody for the treatment of postoperative recurrence and metastasis, with regional lymphadenectomy, in a murine model of cancer. Subcutaneous AB1-HA mesothelioma tumors were induced in BALB/c mice. Established tumors were surgically excised on day 16, with or without sentinel lymph node removal. On the day of surgery, animals were rechallenged with AB1-HA tumor cells at the surgical site (local recurrence) or the opposite flank (metastasis). Postoperative tumors were treated with anti-CD40 (FGK45) on emergence, delivered either intratumorally, peritumorally, or systemically. Local or systemic anti-CD40 treatment slowed postsurgical metastatic growth relative to untreated controls (P = 0.020) and improved survival from metastasis. Anti-CD40 also retarded the growth of local recurrences (P = 0.004) and improved survival from recurrence. Sentinel lymph node dissection did not impair efficacy (P > 0.05). This study demonstrates that anti-CD40 therapy, given either locally or systemically, may be a powerful and readily translatable adjuvant to cancer surgery, including in cases where regional lymphadenectomy is indicated.

Loss of antigen cross-presentation after complete tumor resection is associated with the generation of protective tumor-specific CD8(+) T-cell immunity.

An incomplete understanding on the effect of surgery on tumor-specific immunity continues to hamper efforts to combine surgery with immunotherapy in the clinic. Herein, we describe the impact of tumor resection on the tumor-specific T-cell response, showing that complete tumor resection is associated with (1) a decline in the amount of cross-presented tumor antigens, (2) a decline of cytolytic tumor-specific CD8(+) T cell activity, and (3) the development of systemic CD8(+) T cell-mediated protective immunity. Our findings are consistent with a model whereby tumor resection releases antitumor CD8(+) T cells from chronic antigen exposure, allowing a gradual differentiation toward functional antitumor memory T cells. This process depends on sentinel lymph nodes, as their removal at the time of surgery was associated with a strong negative effect on survival. We conclude that complete tumor resection provides a unique environment that boosts protective immunological memory and might provide a powerful platform for immunotherapy. Our findings also carry important implications for the design and timing of post-surgery immunotherapeutic regimens.

Primary angiosarcoma of the bladder in a young female.

Our case report pertains to a 32-year-old woman initially presenting with left flank pain and gross haematuria throughout her urinary stream. CT of her kidney/ureter/bladder (CT KUB) revealed ureteric dilatation to the level of the bladder without evidence of renal calculus and subsequently a stent was inserted. She represented a month later with contralateral flank pain, and a transuretheral resection of bladder tumour was performed. Histopathological diagnosis was epithelioid angiosarcoma. Further imaging (MRI pelvis) revealed that the tumour arose from the posterior bladder wall with local invasion and regional lymph node metastasis. Ifosfamide and epirubicin chemotherapy with single-fraction radiotherapy induced significant reduction in tumour bulk, although this initial response was followed by the development of symptoms suggestive of disease progression. She died 19 months after initial diagnosis with persistent pulmonary and vertebral metastases although no autopsy was performed.

The use of the Ki-67 marker in the pathological diagnosis of the epithelioid variant of renal angiomyolipoma.

OBJECTIVE: Epithelioid angiomyolipoma (EAML) is a rare malignant variant of renal angiomyolipoma (AML). There were 34 cases of EAML reported in 25 studies (including this present study) over the past decade. About 68% were females and 32% males. The mean age was 40.1 years, 53% developed metastatic disease after nephrectomy, and eight patients had TSC. All cases are reported positive when stained with HMB-45 which also labels all classical AML. This study evaluates the use of Ki-67 (proliferation marker) in the pathological diagnosis of EAML and distinction from classical AML. METHOD: Immunohistochemical reactions for Ki-67 were generated on multiple representative blocks of tissue obtained from two cases of HMB-45 positive EAML and four cases of classic AML and the percentage of positively staining cells estimated. RESULTS: Both cases of EAML were strongly positive for Ki-67 while all four classic AML were completely negative. CONCLUSION: The Ki67 is a useful marker in which distinguishes the malignant epithelioid variant of AML from classic AML.