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Gil-Martin, MAuthorRomeo, MAuthorBarretina-Ginesta, MpAuthor

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November 21, 2024
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Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/MINOVA Study)

Publicated to: CLINICAL CANCER RESEARCH. 30 (1): 176-186 - 2024-01-01 30(1), DOI: 10.1158/1078-0432.CCR-23-0771

Authors:

Tavira, B; Iscar, T; Manso, L; Santaballa, A; Gil-Martin, M; García García, Y; Romeo, M; Iglesias, M; Ferré, AD; Barretina-Ginesta, MP; Manzano, A; Gaba, L; Rubio, MJ; de Andrea, CE; González-Martín, A
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Affiliations

Canc Ctr Clin Univ Navarra, Dept Med Oncol - Author
Canc Ctr Clin Univ Navarra, Dept Pathol - Author
Ctr Invest Biomed Red Canc CIBERONC - Author
Hosp 12 Octubre, Dept Med Oncol - Author
Hosp Clin Barcelona, Dept Med Oncol - Author
Hosp Clin San Carlos, Dept Med Oncol - Author
Hosp Marques de Valdecilla, Dept Med Oncol - Author
Hosp Son Llatzer, Dept Med Oncol - Author
Hosp Univ & Politecn La Fe, Dept Med Oncol - Author
Hosp Univ Reina Sofia, Dept Med Oncol - Author
Inst Catala Oncol Badalona, Dept Med Oncol - Author
Inst Catala Oncol Girona, Dept Med Oncol - Author
Inst Catala Oncol LHosp, Dept Med Oncol - Author
Univ Autnoma Barcelona, Inst Invest & Innovacio Parc Tauli I3PT, Parc Tauli Parc Tauli Hosp Univ, Dept Med Oncol - Author
Univ Navarra, Sch Med, Dept Pathol Anat & Physiol - Author
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Abstract

Purpose: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. Experimental Design: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. Results: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4(+) T cells, an increase of CD8(+) T cells, and an upregulation in effector/regulatory cell ratio (CD8(+)/CD4(+)FOXP3(+)). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS). Conclusions: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4(+), CD8(+) lymphocyte populations, and CD8(+)/CD4(+)FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer.
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Keywords

Adjuvant chemotherapyAdvanced cancerArticleBevacizumabCancer resistanceCancer survivalCarboplatinCarcinoma, ovarian epithelialCd4+ t lymphocyteCd8+ t lymphocyteCell subpopulationChemotherapy, adjuvantClinical articleClinical outcomeControlled studyCytoreductive surgeryEfficacyFemaleForkhead transcription factorForkhead transcription factorsHumanHuman cellHuman tissueHumansImmunofluorescenceImmunohistochemistryInfiltrationMulticenterMultiple cycle treatmentNeoadjuvant chemotherapyNeoadjuvant therapyOvarian neoplasmsOvary cancerOvary carcinomaOvary tumorPaclitaxelPathologyProceduresProgression free survivalRegulatory t lymphocyteSafetySurgeryT-cellsTranscription factor foxp3TrialTumor microenvironmentTumor-associated macrophage

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal CLINICAL CANCER RESEARCH due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 29/328, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-07:

  • WoS: 9
  • Scopus: 9
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 8.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 8 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 4.
  • The number of mentions on the social network X (formerly Twitter): 5 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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