Abstract
ObjectiveAdaptive immune effectors do not influence prognosis in vulvar squamous cell carcinoma (vSCC). Therefore, we tried to clarify the prognostic role of innate immunity and granzyme B-dependent cytotoxicity as defined by intratumoral infiltrates of natural killer cells (CD56+) and lymphocytes expressing granzyme B (GrB+).MethodsWe analyzed 76 primary vSCCs and 35 lymph node metastases that were obtained from 76 patients with a full clinical history. The distribution and density of GrB+ and CD56+ cells within cancer tissues were evaluated by immunohistochemistry and correlated with clinicopathological features, commonly recognized prognostic factors and overall survival (OS).ResultsCD56+ cells were mostly detected within the cancer nests, while GrB+ cells were predominant in the tumor stroma. Intraepithelial (IE) CD56+ infiltrates at the primary site were correlated with depth of invasion (r = 0.339, p = 0.003) and recurrence (r = 0.295, p = 0.011), while IE GrB+ infiltrates were correlated with tumor grade (r = 0.304, p = 0.009) and age (r = 0.333, p = 0.004). The primary cancer nests of metastatic patients were infiltrated more by intraepithelial (IE) CD56+ cells than were those of the non-metastatic patients (p = 0.05). The median OS was 41.16 months (range 1.7–98.43). High IE GrB+ infiltrates predicted longer OS among patients without metastases (p = 0.028). High IE CD56+ infiltrates were correlated with longer OS in metastatic cases (p = 0.009).ConclusionThe combined cytotoxicity of innate and adaptive immune effectors infiltrating cancer nests (IE GrB+) predicts an improved clinical outcome among non-metastatic vSCC patients. The functional status of prognostic IE CD56+ infiltrates in immune escaped (metastatic) tumors requires further investigation.
Highlights
Vulvar cancer has an incidence of 1–2 per 100,000 women per year and represents 3–5 % of all gynecological malignancies [1,2,3]
CD8 + lymphocytes represent an important subpopulation of cytotoxic T lymphocytes and are the most likely effector Tumor infiltrating lymphocytes (TILs) of adaptive anti-tumor immunity [9]
The clinico-pathological characteristics of this group were carefully described in our two previous manuscripts analyzing the expression of indoleamine 2,3-dioxygenase (IDO) and the infiltration of CD8+, CD4+ and FOXP3+ T lymphocytes in vulvar squamous cell carcinoma (vSCC) [14, 15]
Summary
Vulvar cancer has an incidence of 1–2 per 100,000 women per year and represents 3–5 % of all gynecological malignancies [1,2,3]. Squamous cell carcinoma (SCC) is the predominant malignancy at this site, accounting for approximately 85–90 % of vulvar cancers [4, 5]. Treatment of advanced stage (FIGO III and IV) vulvar cancer patients may be ineffective, even with chemotherapy and radiotherapy [6, 7]. Tumor infiltrating lymphocytes (TILs) are considered to be a manifestation of the host immune response against cancer cells [8]. CD8 + lymphocytes represent an important subpopulation of cytotoxic T lymphocytes and are the most likely effector TILs of adaptive anti-tumor immunity [9]
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