Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer

Bösmüller, H.; Wagner, Philipp; Peper, Janet Kerstin; Schuster, Heiko; Pham, Deborah Lam; Greif, Karen F.; Beschorner, Christine; Rammensee, Hans‐Georg; Stevanović, Stefan; Fend, Falko; Staebler, Annette

doi:10.1097/igc.0000000000000672

Cited by 72 publications

(69 citation statements)

References 31 publications

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“…First, we confirmed the recent reports on the prognostic benefit of CD103+ TIL in HGSC [7,11] in an independent cohort of advanced-stage HGSC patients treated with either primary surgery and adjuvant chemotherapy (PS; n=84), or neo-adjuvant chemotherapy followed by interval surgery (NACT; n=102) [12]. CD3+, CD8+ and CD103+ TIL were present in tumors from most patients and the distribution of CD3+ and CD8+ TIL in tumor epithelium and stroma was similar (Figure 1A).…”

Section: Resultssupporting

confidence: 89%

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

et al. 2016

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CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis. We further demonstrate that CD103+ TIL were almost exclusively CD3+ TCRαβ+ CD8αβ+ CD4- T cells, but heterogeneously expressed T cell memory and differentiation markers. Activation of peripheral T cells in the presence of HGSC was sufficient to trigger induction of CD103 in over 90% of all CD8+ cells in a T cell receptor (TCR)- and TGFβR1-dependent manner. Finally, CD103+ TIL isolated from primary HGSC showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27. Taken together, our data indicate CD103+ TIL in HGSC are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition.

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Section: Resultssupporting

confidence: 89%

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

et al. 2016

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“…Webb et al have demonstrated that the integrin CD103, which binds to E-cadherin expressed by epithelial cells, is highly expressed by intra-epithelial effector T cells in ovarian carcinoma, and suggested that it is these CD103 + T cells that contribute to the improved prognosis seen with high levels of TILs [201]. Similarly, Bosmuller et al found CD103 added prognostic value to conventional T cell markers in the assessment of TILs in ovarian carcinoma [202]. However, two studies have reported important prognostic value of TILs in the stromal compartment, similar to that seen in the epithelial compartment [203,204].…”

Section: Tils In Gynecological Carcinomasmentioning

confidence: 99%

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Hendry

Salgado

Gevaert

et al. 2017

Advances in Anatomic Pathology

611

366

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Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

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“…This cohort has been published previously. 18 Age, stage, and response rates to platinum-based chemotherapy are within the expected range. As expected, platinum sensitivity was the strongest predictor of prognosis.…”

Section: Immunohistochemical Findingsmentioning

confidence: 93%

“…The construction of the TMAs was performed as recently published. 17,18 Each case was represented by six cores, three from each side in the case of bilateral tumors, and 3 each from 2 different areas in unilateral tumors, with 0.6 mm diameter, punched with a semiautomatic tissue array instrument (Beecher Instruments Sun Prairie, WI). Cores with 1.0 mm diameter were used for low-grade serous carcinoma (LGSOCs) and serous borderline tumors.…”

Section: Tma and Immunohistochemistrymentioning

confidence: 99%

CD56 (Neural Cell Adhesion Molecule) Expression in Ovarian Carcinomas: Association With High-Grade and Advanced Stage But Not With Neuroendocrine Differentiation

Bösmüller

Wagner²,

Pham³

et al. 2017

Int J Gynecol Cancer

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Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer

Abstract: These results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.

Cited by 72 publications

References 31 publications

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

CD56 (Neural Cell Adhesion Molecule) Expression in Ovarian Carcinomas: Association With High-Grade and Advanced Stage But Not With Neuroendocrine Differentiation

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