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Query: "author" (Cvetka Grašič-Kuhar) .

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Immune infiltration, effector T-cell enrichment, and functional context for prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer
Ana Demšar, Klara Geršak, Barbara Gazić, Tanja Blagus, Katja Goričar, Gregor Jezernik, Vita Dolžan, Cvetka Grašič-Kuhar, 2026, original scientific article

Abstract: Tumor-infiltrating lymphocytes (TILs) are an established predictor of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer. However, TILs primarily reflect the extent of immune infiltration and provide limited insight into immune functional state. We investigated whether integrating measures of immune infiltration (TILs), effector T-cell presence (CD8), and functional context (immune checkpoint components) may improve prediction of pCR beyond TILs alone. Pretreatment tumor biopsies from 166 patients with early breast cancer treated with standard NACT were assessed for stromal TILs and mRNA expression of CD8, PD-1, LAG-3, and TIM-3. Associations with pCR were evaluated using univariate and multivariable logistic regression, and composite immune phenotypes were constructed to capture functional immune states. In univariate analyses, higher TILs, CD8, PD-1, and LAG-3 were associated with pCR (all p < 0.05), whereas TIM-3 was not (p = 0.801). In multivariable models, TILs remained independently associated with pCR when adjusted for checkpoint markers, but this association was attenuated when CD8 was included, consistent with the strong biological correlation between TILs and CD8, and neither CD8 nor checkpoint markers retained independent significance. PD-1 and LAG-3 expression strongly correlated with CD8 and moderately correlated with TILs, indicating that checkpoint expression predominantly reflects an immune effector-engaged tumor microenvironment. Composite immune phenotypes based on CD8/PD-1 co-expression identified distinct immune functional states, with CD8-high/PD-1-high tumors demonstrating the highest pCR rates. Hierarchical modeling showed modest improvements in discrimination with sequential addition of immune variables to clinical predictors, with the integrative CD8/PD-1 model achieving the highest discrimination within the cohort (AUC = 0.849), although the magnitude of improvement beyond TIL assessment alone was limited. In conclusion, immune infiltration, effector T-cell presence, and functional immune context represent complementary dimensions for pCR prediction following NACT in breast cancer. However, TILs remain the most robust and clinically feasible immune biomarker.
Keywords: PD-1 immune checkpoint, breast cancer, immune microenvironment, neoadjuvant chemotherapy
Published in DiRROS: 20.04.2026; Views: 150; Downloads: 111
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Klinični pomen cirkulirajočih tumorskih celic pri raku dojk
Cvetka Grašič-Kuhar, 2025, published scientific conference contribution abstract

Keywords: rak dojke, cirkulirajoče tumorske celice, klinična onkologija
Published in DiRROS: 11.03.2026; Views: 233; Downloads: 100
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Induction chemotherapy and concurrent chemoradiotherapy for larynx preservation in laryngeal and hypopharyngeal cancer
Primož Strojan, Gaber Plavc, Robert Šifrer, Simona Jereb, Boštjan Lanišnik, Marko Kokalj, Aleš Grošelj, Cvetka Grašič-Kuhar, 2025, original scientific article

Abstract: To test the hypothesis that clinical tumor response after a single cycle of induction chemotherapy (ICT) can reliably differentiate between chemo-/radiosensitive and resistant tumors in the larynx preservation setting. Patients and methods Treatment consisted of docetaxel/cisplatin/5-fluorouracil (TPF) ICT followed by concurrent chemoradiotherapy (cCRT) with weekly cisplatin. The response of the primary tumor was assessed by transnasal endoscopy after the first ICT cycle. Results 37/39 (95%) patients with laryngeal (46%) or hypopharyngeal (54%) carcinoma responded to one cycle of ICT, and two patients were referred for salvage surgery. Laryngectomy-free survival at 2 and 5 years was 87% and 75%, respectively. The corresponding rates for locoregional control (and also for disease-free survival) were 79% and 70% and for overall survival 92% and 82%. Conclusions Clinical assessment of tumor response to one cycle of TPF ICT serves as a valid and easy-to-use predictor of tumor sensitivity to platinum-based cCRT.
Keywords: induction chemotherapy, chemoradiotherapy, arynx preservation
Published in DiRROS: 16.01.2026; Views: 345; Downloads: 367
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Association of tumor-infiltrating lymphocytes and inflammation status with survival outcome in patients with high-grade serous ovarian carcinoma
Simona Miceska, Cvetka Grašič-Kuhar, Snježana Frković-Grazio, Erik Škof, Praveen Krishnamoorthy, Dineo Khabele, Veronika Kloboves-Prevodnik, 2025, original scientific article

Abstract: In this study, we investigated the association between tumor-infiltrating lymphocytes (TILs), inflammation status, and progression-free survival (PFS) in patients with primary high-grade serous ovarian carcinoma (HGSC). We assessed the percentages of different intraepithelial and stromal TIL subtypes using both manual and digital methods, following established recommendations for TIL assessment. In addition, we evaluated inflammation status through several immune scores, including the pan-immune-inflammation value (PIV). Our results suggest that stromal CD3+ and CD8+ TILs, as well as PIV, may serve as potential prognostic indicators in HGSC, as they remained potential independent markers in multivariate analysis.
Keywords: ovarian carcinoma, high-grade serous ovarian carcinoma, prognostic factors
Published in DiRROS: 05.12.2025; Views: 976; Downloads: 167
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