Prognostic markers for survival in patients with metastatic renal cell carcinoma treated with interleukin-2

Abstract

Interleukin-2 (IL-2)-based immunotherapy can induce antitumor responses in about 25% of patients with metastatic renal cell carcinoma (RCC). The limited effect and the severe side-effects of IL-2 have led us to perform a prognostic factor analysis. Twenty-four patients with metastatic RCC were treated with IL-2. Flow cytometry and immunohistology were used to determine DNA ploidy, HLA-II expression on tumor cells, and the presence of macrophages in the primary tumor. These variables were examined in relation to survival. The 4-year overall survival rate was 38%. Forty-six percent of the primary tumors were aneuploid. All tumors, except one, showed HLA-II expression and macrophage presence. A statistically significant correlation (r = 0.66, P = 0.002) was found between HLA-II expression and macrophage presence. Patients with high HLA-II expression had a lower 4-year survival (22% compared to 50%), as had patients with high macrophage presence (20% compared to 42%). Of note, patients characterized by both high HLA-II and high macrophage expression had the worst survival (13% compared to 50%). We concluded that DNA ploidy was not predictive for survival, whereas HLA-II expression and macrophage presence may represent valuable prognostic factors related to survival. The present data suggest that more of the patients with no or moderate HLA-II expression and/or no or moderate macrophage presence in the primary tumor could survive with persistence of their malignant disease after having received IL-2 immunotherapy, as compared to patients with both high HLA-II and high macrophage expression.

Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma

“…Prognostic factors and predictive algorithms for overall and disease‐specific survival in patients with RCC have been reported previously by multiple investigators 8–19. However, to our knowledge, no models exist that can predict patient survival after nephrectomy and immunotherapy treatment for metastatic RCC.…”

Urological malignancies and the proteomic-genomic interface

“…The standard therapies of metastatic disease are interleukin-2 and interferon-a [9] but although promising, objective response rates are only approximately 20% [10]. There is no reliable marker to determine which patients will respond to these therapies, although candidate markers include histocompatibility antigen II (HLA-II) expression, intratumoral macrophage infiltration [11], as well as circulating levels of interleukin-6 [12] and soluble interleukin-2 receptor [13].…”

One Hundred Years of Cancer Immunotherapy: A Critical Appraisal

“…Patients with metastatic renal cell carcinoma with no or moderate HLA-II expression and/ or no or moderate macrophage presence in the tumor could survive with their persistent malignant disease after having received IL-2 immunotherapy. In contrast, patients with both high HLA-II and high macrophage expression were not affected by this treatment [105]. In view of the results obtained in experimental tumor models showing the effectiveness of immunotherapy with antibody-targeted IL-2 [42,43,[63][64][65], the effectiveness of antibody-targeted IL-2 was assayed in vitro to enhance the ability of a tumor-infiltrating lymphocyte line against an autologous GD 2 -expressing melanoma cells [106].…”