Status of cellular immunity lacks prognostic significance in vulvar squamous carcinoma

Jong, Renske A. de; Toppen, N. L.; Hoor, Klaske A. ten; Boezen, H. Marike; Kema, Ido P.; Hollema, Harmen; Nijman, Hans W.

doi:10.1016/j.ygyno.2011.12.416

Cited by 22 publications

(25 citation statements)

References 34 publications

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“…Lack of prognostic significance of adaptive immune effectors and regulatory T cells described by others [31] was previously confirmed by our group for nearly the same cohort [19, 20]. All these findings have suggested no place for immunotherapy for vulvar cancer patients.…”

Section: Discussionsupporting

confidence: 79%

Local immune response depends on p16INK4a status of primary tumor in vulvar squamous cell carcinoma

2017

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BackgroundThe p16Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a-overexpression itself is an independent prognostic factor for vulvar cancer.AimTo determine significance of the tumor infiltrating immune cells and p16Ink4a–status for better outcome of patients with vulvar cancer.MethodsIntraepithelial tumor infiltrating lymphocytes: CD8+, CD4+, FOXP3+, CD56+, tumor associated macrophages: CD68+, and GZB+ cells were calculated in 85 vulvar squamous cell carcinomas with previously defined p16Ink4a and high-risk HPV-status. Number of intraepithelial CD8+, CD4+, FOXP3+, CD56+, CD68+ and GZB+ cells were compared between tumors with different p16INK4a status and overlapping high-risk HPV-status separately. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model.Resultsp16Ink4a-negative tumors were more infiltrated by intraepithelial CD8+, CD4+ and GZB+ cells than p16Ink4a-positive tumors (p=0.032, p=0.016 and p=0.007 respectively). High-risk HPV-status did not correlate with the infiltration of immune cells. Median follow up was 89.20 months (range 1.7-189.5). High CD4+ and CD56+ indices were correlated with prognosis in p16Ink4a–positive cases (p=0.039 and p=0.013 respectively). Low CD68+ infiltrates were correlated with prognosis in p16Ink4a-negative cases (p=0.018). Conclusion: p16Ink4a-status impacts local immune surveillance as represented by tumor infiltrating immune cells. Immunologic effects contributing to clinical outcome might depend on p16Ink4a-overexpression.

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Section: Discussionsupporting

confidence: 79%

Local immune response depends on p16INK4a status of primary tumor in vulvar squamous cell carcinoma

2017

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“…This could explain the lack of prognostic significance of CD8+ lymphocytes in vSCC [15, 16] and suggests that the number of TILs present in the stroma probably provides a better indication of coexisting inflammatory processes than the immunogenicity of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the status of adaptive immunity represented by CD8+, CD4+ and FOXP3+ T cells was found to lack prognostic significance in vSCC [14–16]. Therefore, the purpose of this study was to clarify the prognostic roles of innate immune effectors represented by CD56+ cells and granzyme B-dependent cytolysis.…”

Section: Introductionmentioning

confidence: 99%

Subtypes of cytotoxic lymphocytes and natural killer cells infiltrating cancer nests correlate with prognosis in patients with vulvar squamous cell carcinoma

Sznurkowski

Żawrocki

Biernat

2013

Cancer Immunol Immunother

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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.

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“…71). The reported prognostic value of FoxP3þ T cells in these 58 studies ranged from poor (n ¼ 23), to neutral (n ¼ 23), to good (n ¼ 12).…”

Section: Introductionmentioning

confidence: 98%

Deciphering the Adaptive Immune Response to Ovarian Cancer

Nelson¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)Oct 2013 REPORT TYPE Annual DATES COVERED (From -To PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERBritish Columbia Cancer Agency, 2410 Lee Avenue, Victoria BC V8R 6V5 Canada SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) US Army Medical Research and Material Command Fort Detrick, Maryland SPONSOR/MONITOR'S REPORT 21702-5012 NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTThe presence of CD8+ tumor-infiltrating lymphocytes (CD8+ TIL) has been associated with increased patient survival in ovarian cancer. We discovered that this effect is even stronger when CD8+ TIL are found together with CD20+ B cells and CD4+FoxP3+ T cells. We hypothesized that CD20+ TIL contribute to tumor immunity by presenting antigens to CD4+ and CD8+ TIL. To test this, we are attempting to identify the tumor antigens recognized by CD20+ TIL. As a first step, this year we developed methods to clone immunoglobulin molecules from individual CD20+ TIL by single-cell reverse-transcriptase PCR. We also hypothesized that a subset of CD4+FoxP3+ TIL produces effector cytokines that enhance CD8+ TIL responses. This year, we developed methods to profile T cell receptors (TCR) from tumor-infiltrating T cells, which will facilitate future TCR cloning and antigen identification, as originally proposed. Overall, this project is progressing on schedule and is yielding innovative methods and publishable results that lead toward a better understanding of the mechanisms used by the immune system to control the progression of ovarian cancer. SUBJECT TERMS INTRODUCTION:Tumor-infiltrating CD8+ T cells are strongly associated with increased survival in ovarian cancer. However, they do not work in isolation. We discovered that two other types of immune cell play an important supportive role: B cells and helper T cells (specifically, helper T cells that express a protein called FoxP3). We made this discovery by performing a systematic analysis of immune cells in ovarian...

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Status of cellular immunity lacks prognostic significance in vulvar squamous carcinoma

Cited by 22 publications

References 34 publications

Local immune response depends on p16INK4a status of primary tumor in vulvar squamous cell carcinoma

Local immune response depends on p16INK4a status of primary tumor in vulvar squamous cell carcinoma

Subtypes of cytotoxic lymphocytes and natural killer cells infiltrating cancer nests correlate with prognosis in patients with vulvar squamous cell carcinoma

Deciphering the Adaptive Immune Response to Ovarian Cancer

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