The impact of T‐cell immunity on ovarian cancer outcomes

Nelson, Brad H.

doi:10.1111/j.1600-065x.2008.00614.x

Cited by 144 publications

(131 citation statements)

References 178 publications

(262 reference statements)

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“…16,17 Tumors from women with high-grade serous cancers frequently show a host immune response, and the presence of cytotoxic T lymphocytes, and T-regulatory cells is consistently associated with favorable prognosis. [18][19][20][21][22][23][24] Germline mutations in BRCA1 and BRCA2 are present in B18% of ovarian cancer patients with high-grade serous carcinoma. [25][26][27] When combined with BRCA deficiencies that result from somatic mutations or epigenetic silencing, it appears that up to half of all high-grade serous ovarian cancers (hereditary and sporadic) have BRCA dysfunction.…”

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confidence: 99%

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

et al. 2012

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We characterized BRCA1 and BRCA2 status (mutation/methylation) in a consecutive series of cases of ovarian carcinoma in order to identify differences in clinicopathological features, molecular characteristics, and outcome between the pelvic high-grade serous cancers with (i) germline or somatic mutations in BRCA1 or BRCA2, (ii) methylation of BRCA1, and (iii) normal BRCA1 or BRCA2. In all, 131 women were identified prospectively, who were undergoing surgical staging and agreed to germline testing for BRCA1 and BRCA2 mutations. Histopathology, germline and somatic BRCA1 or BRCA2 mutations, BRCA1 methylation, and BRCA1 and BRCA2 mRNA expression levels distinguished four subgroups. In all, 103 cases were high-grade serous carcinoma and of these 31 (30%) had germline or somatic BRCA1 or BRCA2 mutations (20% BRCA1 and 10% BRCA2) (group 1), 21 (20%) had methylation of BRCA1 (group 2), and in 51 (50%) there was no BRCA loss (group 3). Group 4 consisted of 28 cases of non-high-grade serous, none of which had BRCA loss. BRCA1 and BRCA2 mRNA expression levels correlated with designated group (P ¼ 0.0008). Among high-grade serous carcinomas, there were no differences between groups 1-3 with respect to stage, ascites, CA125 level, platinum sensitivity, cytoreduction rate, neoadjuvant chemotherapy, or survival. Tumors with BRCA1 or BRCA2 mutations had increased immune infiltrates (CD20 and TIA-1) compared with high-grade serous without mutations (P ¼ 0.034, 0.027). TP53 expression differed between groups (Po0.0001), with abnormal TP53 expression in 49/50 tumors from groups 1 and 2. Wild-type TP53 expression was associated with worse outcome in high-grade serous (Po0.001). BRCA loss (mutation/methylation) is a common event in the pelvic high-grade serous (50%). TP53 abnormalities and increased immune cell infiltrates are significantly more common in high-grade serous with germline and somatic mutations in BRCA1 or BRCA2, compared with tumors lacking BRCA abnormalities.

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confidence: 99%

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

et al. 2012

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“…This is in favor of the concept of partial degradation and thus widening of the collagen network for increased T-cell migration [29]. More T-lymphocyte infiltration, especially CD3+CD8+ lymphocytes will result in a better prognosis for the patients [25]. In our advanced-stage patients, we found significantly more CD8+ lymphocytes in stroma.…”

Section: Page 5 Ofmentioning

confidence: 73%

“…After each incubation step, slides were washed two times with phosphate buffered saline (PBS). Zhang et al on clinical characteristics, we followed their methodology in the number and selection of fields and markers despite newer insights into the markers for regulatory T cells [19,25].…”

Section: Semiquantitative Immunohistochemistrymentioning

confidence: 99%

Differential Associations of MMP-2 and MMP-14 with Stromal Amounts and T lymphocyte Presence in Ovarian Cancer

Vos¹,

Bekers²

2016

J Mol Genet Med

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“…18,[23][24][25] Similarly, Nelson recently established that OC induces a host immune response involving T-cells, which prolong OS. 26 Unfortunately, this observation was not confirmed by comparison of times to progression between cGvHD and nonecGvHD patients, which was not significant.…”

Section: Discussionmentioning

confidence: 90%

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Bay¹,

Cabrespine-Faugeras²,

Tabrizi³

et al. 2010

Intl Journal of Cancer

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Although preliminary results suggest that allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the low patient number in previous studies had limited ability to evaluate the true benefit of allo HCT in OC. This retrospective multicenter study included 30 patients with OC allografted between 1995 and 2005 to determine the outcome of patients with OC treated with allo HCT. Prior to allo HCT, patients were in complete response (n 5 1), partial response (n 5 7), stable disease (n 5 11) or had progressive disease (n 5 13). An objective response (OR) was observed in 50% (95% CI, 33-67) of patients. Three patients of responding patients had an objective response following the development of acute graft-versus-host disease (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18-50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year, respectively. With a median follow-up of 74.5 months (range 16-148), median progression free survival (PFS) was 6 months and median overall survival (OS) was 10.4 months. Patients who developed cGvHD following allo HCT had a significant OS improvement compared to those who did not (17.6 months vs. 6.5 months, p 5 0.042). However, PFS was not similarly significantly improved in patients who developed cGvHD (12 months versus 3.7 months, p 5 0.81). Allo HCT in OC may lead to graft-versus-OC effects. Their clinical relevance remains to be shown.Ovarian cancer (OC), the fifth-leading cause of death for women in the United States and Europe, is the most deadly of the gynecologic malignancies. 1 Current systemic therapy consists of a combination of carboplatin and paclitaxel. Even after extensive surgery and chemotherapy, up to 50% of patients suffer from relapsing disease. Median overall survival (OS) for patients after recurrence is $2 years. 2 To improve outcome, high-dose chemotherapy regimens have been tried usually based on carboplatin combinations. These appear to delay relapse but have no influence on OS. [3][4][5] Allogeneic hematopoietic stem cell transplantation (allo HCT) is an effective therapy for many hematological malignancies. The therapeutic benefit of allogeneic transplantation relies not only on high-dose chemotherapy administered before transplantation but also is largely related to an immune-mediated graft-versus-leukemia effect, due to transplantation of the donor's immune system along with the hematopoietic tissue. Recent data from experimental animal models and from preliminary clinical experience suggest that a graft-versus-tumor effect, analogous to the graft-versusleukemia effect, may be generated against solid tumors such as renal cell cancer, breast cancer and OC. 6 Regarding OC, immunotherapy agents such as systemic or intraperitoneal interleukin-2 7-9 and adoptive transfer of tumor-infiltrating lymphocytes 10 have been used with success, testifying to the

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The impact of T‐cell immunity on ovarian cancer outcomes

Cited by 144 publications

References 178 publications

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

Differential Associations of MMP-2 and MMP-14 with Stromal Amounts and T lymphocyte Presence in Ovarian Cancer

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

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