Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Maartje C. A. Wouters; Fenne L. Komdeur; Hagma H. Workel; Harry G. Klip; Annechien Plat; Neeltje M. Kooi; G. Bea A. Wisman; Marian J. E. Mourits; Henriette J. G. Arts; Maaike H. M. Oonk; Refika Yigit; Steven de Jong; Cornelis J. M. Melief; Harry Hollema; Evelien W. Duiker; Toos Daemen; Marco de Bruyn; Hans W. Nijman

doi:10.1158/1078-0432.CCR-15-1617

Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Maartje C. A. Wouters, Fenne L. Komdeur, Hagma H. Workel, Harry G. Klip, Annechien Plat, Neeltje M. Kooi, G. Bea A. Wisman, Marian J. E. Mourits, Henriette J. G. Arts, Maaike H. M. Oonk, Refika Yigit, Steven de Jong, Cornelis J. M. Melief, Harry Hollema, Evelien W. Duiker, Toos Daemen, Marco de Bruyn, Hans W. Nijman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

31 Citations (Scopus)

Abstract

Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy.

Experimental Design: Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence.

Results: A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (

Conclusions: Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials. (C) 2015 AACR.

Original language	English
Pages (from-to)	714-724
Number of pages	11
Journal	Clinical Cancer Research
Volume	22
Issue number	3
DOIs	https://doi.org/10.1158/1078-0432.CCR-15-1617
Publication status	Published - 1-Feb-2016

Keywords

NEGATIVE BREAST-CANCER
NEOADJUVANT CHEMOTHERAPY
MONOCLONAL-ANTIBODY
IN-VIVO
SURVIVAL
SURGERY
IMMUNOTHERAPY
RESPONSES
EFFECTOR

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Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer
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Wouters, M. C. A., Komdeur, F. L., Workel, H. H., Klip, H. G., Plat, A., Kooi, N. M., Wisman, G. B. A., Mourits, M. J. E., Arts, H. J. G., Oonk, M. H. M., Yigit, R., de Jong, S., Melief, C. J. M., Hollema, H., Duiker, E. W., Daemen, T., de Bruyn, M., & Nijman, H. W. (2016). Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer. Clinical Cancer Research, 22(3), 714-724. https://doi.org/10.1158/1078-0432.CCR-15-1617

Wouters, Maartje C. A. ; Komdeur, Fenne L. ; Workel, Hagma H. ; Klip, Harry G. ; Plat, Annechien ; Kooi, Neeltje M. ; Wisman, G. Bea A. ; Mourits, Marian J. E. ; Arts, Henriette J. G. ; Oonk, Maaike H. M. ; Yigit, Refika ; de Jong, Steven ; Melief, Cornelis J. M. ; Hollema, Harry ; Duiker, Evelien W. ; Daemen, Toos ; de Bruyn, Marco ; Nijman, Hans W. / Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 3. pp. 714-724.

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title = "Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer",

abstract = "Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy.Experimental Design: Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence.Results: A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (Conclusions: Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials. (C) 2015 AACR.",

keywords = "NEGATIVE BREAST-CANCER, NEOADJUVANT CHEMOTHERAPY, MONOCLONAL-ANTIBODY, IN-VIVO, SURVIVAL, SURGERY, IMMUNOTHERAPY, RESPONSES, EFFECTOR",

author = "Wouters, {Maartje C. A.} and Komdeur, {Fenne L.} and Workel, {Hagma H.} and Klip, {Harry G.} and Annechien Plat and Kooi, {Neeltje M.} and Wisman, {G. Bea A.} and Mourits, {Marian J. E.} and Arts, {Henriette J. G.} and Oonk, {Maaike H. M.} and Refika Yigit and {de Jong}, Steven and Melief, {Cornelis J. M.} and Harry Hollema and Duiker, {Evelien W.} and Toos Daemen and {de Bruyn}, Marco and Nijman, {Hans W.}",

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doi = "10.1158/1078-0432.CCR-15-1617",

language = "English",

volume = "22",

pages = "714--724",

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Wouters, MCA, Komdeur, FL, Workel, HH, Klip, HG, Plat, A, Kooi, NM, Wisman, GBA , Mourits, MJE , Arts, HJG, Oonk, MHM, Yigit, R, de Jong, S, Melief, CJM, Hollema, H , Duiker, EW , Daemen, T , de Bruyn, M & Nijman, HW 2016, 'Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer', Clinical Cancer Research, vol. 22, no. 3, pp. 714-724. https://doi.org/10.1158/1078-0432.CCR-15-1617

Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer. / Wouters, Maartje C. A.; Komdeur, Fenne L.; Workel, Hagma H.; Klip, Harry G.; Plat, Annechien; Kooi, Neeltje M.; Wisman, G. Bea A.; Mourits, Marian J. E.; Arts, Henriette J. G.; Oonk, Maaike H. M.; Yigit, Refika; de Jong, Steven; Melief, Cornelis J. M.; Hollema, Harry ; Duiker, Evelien W.; Daemen, Toos ; de Bruyn, Marco ; Nijman, Hans W.

In: Clinical Cancer Research, Vol. 22, No. 3, 01.02.2016, p. 714-724.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

AU - Wouters, Maartje C. A.

AU - Komdeur, Fenne L.

AU - Workel, Hagma H.

AU - Klip, Harry G.

AU - Plat, Annechien

AU - Kooi, Neeltje M.

AU - Wisman, G. Bea A.

AU - Mourits, Marian J. E.

AU - Arts, Henriette J. G.

AU - Oonk, Maaike H. M.

AU - Yigit, Refika

AU - de Jong, Steven

AU - Melief, Cornelis J. M.

AU - Hollema, Harry

AU - Duiker, Evelien W.

AU - Daemen, Toos

AU - de Bruyn, Marco

AU - Nijman, Hans W.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy.Experimental Design: Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence.Results: A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (Conclusions: Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials. (C) 2015 AACR.

AB - Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy.Experimental Design: Tissue microarray slides containing samples of 171 patients were analyzed for CD8(+) TIL by IHC. Freshly isolated CD8(+) TIL subsets were characterized by flow cytometry based on differentiation, activation, and exhaustion markers. Relevant T-cell subsets (CD27(+)) were validated using IHC and immunofluorescence.Results: A prognostic benefit for patients with high intratumoral CD8(+) TIL was observed if primary surgery had resulted in a complete cytoreduction (no residual tissue). By contrast, optimal (Conclusions: Our findings indicate that treatment regimen, surgical result, and the differentiation of TIL should all be taken into account when studying immune factors in HGSC or, by extension, selecting patients for immunotherapy trials. (C) 2015 AACR.

KW - NEGATIVE BREAST-CANCER

KW - NEOADJUVANT CHEMOTHERAPY

KW - MONOCLONAL-ANTIBODY

KW - IN-VIVO

KW - SURVIVAL

KW - SURGERY

KW - IMMUNOTHERAPY

KW - RESPONSES

KW - EFFECTOR

U2 - 10.1158/1078-0432.CCR-15-1617

DO - 10.1158/1078-0432.CCR-15-1617

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VL - 22

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JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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