关键词: advanced solid cancer immune evasion immunotherapy minimal residual disease tumor burden

Mesh : Adult Aged Antineoplastic Agents / administration & dosage therapeutic use Breast Neoplasms / drug therapy pathology Celecoxib / administration & dosage therapeutic use Colonic Neoplasms / drug therapy pathology Cyclooxygenase 2 Inhibitors / administration & dosage therapeutic use Cyclophosphamide / administration & dosage therapeutic use Dexamethasone / administration & dosage therapeutic use Diterpenes / administration & dosage therapeutic use Female Humans Immunosuppressive Agents / administration & dosage therapeutic use Interleukins / blood Male Middle Aged Neoplasm Metastasis Prostatic Neoplasms / drug therapy pathology Retinyl Esters Tumor Burden Tumor Escape Vitamin A / administration & dosage analogs & derivatives therapeutic use Vitamins / administration & dosage therapeutic use alpha-Tocopherol / administration & dosage therapeutic use

来  源:   DOI:10.3390/ijms20235986   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
This article summarizes the histories of six patients with different solid tumors treated with a new strategy based on tumor burden reduction and immune evasion as potential targets. All six patients were at a high risk of relapse and were likely to have a minimal residual disease following conventional therapy: biochemical recurrence (BCR) following radical prostatectomy (RP) (two prostate cancers patients), removal of distant metastases (one colorectal and one breast cancer), and complete response (CR) of distant metastases to conventional therapy (one breast cancer and one esophageal-gastric junction cancer). Four of the patients, two after RP and BCR, one after removal of a single pulmonary metastasis from breast cancer, and one after CR to chemotherapy of peritoneal metastases and ascites from an esophageal-gastric junction primary cancer, regularly received cycles of a new drug schedule with the aim of inhibiting immune suppression (IT). In these four patients, preliminary laboratory tests of peripheral blood suggested an interleukin (IL)-2/IL-12 mediated stimulation of cellular immune response with a concomitant decrease in vascular endothelial growth factor (VEGF) immune suppression. The fifth case was a breast cancer patient with distant metastases in CR, while receiving beta-interferon and interleukin-2 in addition to conventional hormone therapy. To date, all five patients are alive and doing well and they have been unexpectedly disease-free for 201 and 78 months following BCR, 28 months following the removal of a single pulmonary metastases, 32 months following CR to chemotherapy of peritoneal metastases and ascites, and 140 months following diagnosis of multiple bone metastases, respectively. The sixth patient, who had colorectal cancer and multiple synchronous liver metastases and underwent nine surgical interventions for metastatic disease, although not disease-free, is doing well 98 months after primary surgery. Our six cases reports can be interpreted with the hypothesis that immune manipulation and/or a concomitant low tumor burden favored their clinical outcome.
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