Research Article
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The Relationship Between Tumor Infiltrating T Lymphocyte Density with Prognostic Factors in Breast Cancer

Year 2025, Volume: 15 Issue: 2, 118 - 127, 30.06.2025
https://doi.org/10.31832/smj.1625190

Abstract

Introduction: Tumor-infiltrating lymphocytes are immune system cells in the tumor microenvironment and play a critical role in the immune response to cancer. In breast carcinoma, it has been demonstrated that the amount of tumor-infiltrating lymphocytes may have prognostic and predictive importance. In our study, inflammatory cells in breast cancer tumor tissues were evaluated considering the TILs Working Group standards and their relationship with the prognostic factors.
Material Method: Mastectomy and breast-conserving surgery materials of 100 patients with the diagnosis of Invasive Carcinoma, No Special Type (NST) who did not receive neoadjuvant chemotherapy and who were examined in the Pathology Department laboratory of Sakarya University Faculty of Medicine between 2011 and 2015 were included in the study and prognostic parameters including lymph node metastasis, tumor diameter stage, histological grade of the tumor, estrogen; progesterone and Her2 receptor status were determined.
Results: Fifty of the cases had lymph node metastasis, while 50 patients did not have lymph node metastasis. When the distribution of patients according to the histological grade of the tumors was examined among the subgroups of variables related to the prognosis of the patients, 24 patients were grade 1, 44 patients were grade 2 and 32 patients were grade 3. A statistically significant positive correlation was observed between the grade 1 and grade 3 groups in terms of intratumoral stromal CD8 positive T lymphocyte infiltration according to different grades.
Conclusion: According to our study, it was determined that the density of CD8(+) T lymphocyte infiltration was higher in tumors with higher grade. Our study is important in terms of creating awareness that the increase in the density of lymphocytes infiltrating the tumor may have prognostic and predictive value.

References

  • Ciarka A, Piatek M, Peksa R, Kunc M, Senkus E. Tumor-infiltrating lymphocytes (TILs) in breast cancer: Prognostic and predictive significance across molecular subtypes. Biomedicines. 2024;12:763.
  • Khoury T, Nagrale V, Opyrchal M, Peng X, Wang D, Yao S. Prognostic significance of stromal versus intratumoral infiltrating lymphocytes in different subtypes of breast cancer treated with cytotoxic neoadjuvant chemotherapy. Appl Immunohistochem Mol Morphol. 2018;26:523.
  • Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating Foxp3+ regulatory T cells. Clin Cancer Res. 2008;14:2413–2420.
  • Gu-Trantien C, Loi S, Garaud S, Equeter C, Libin M, De Wind A et al. CD4+ Follicular helper T cell infiltration predicts breast cancer survival. J Clin Investig. 2013;123:2873–2892.
  • Solinas C, Carbognin L, De Silva P, Criscitiello C, Lambertini M. Tumor-infiltrating lymphocytes in breast cancer according to tumor subtype: Current state of the art. Breast. 2017;35:142–150.
  • Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The Evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann. Oncol. 2015;26:259–271.
  • Menard S, Fortis S, Castiglioni F, Agresti R, Balsari A. HER2 as a prognostic factor in breast cancer. Oncology. 2001;2:67–72.
  • Lee AK, De Lellis RA, Silverman ML, Heatley GJ, Wolfe HJ. Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast. J Clin Oncol. 1990;8(9):1457-1465.
  • Gasparini G et al. Tumor microvessel density, p53 expression, tumor size and peritumoral lymphatic vessel invasion are relevant prognostic markers in node negative breast carcinoma. J Clin Oncol.1994;12(3):454-466.
  • Kato T, Kameoka S, Kimura T, Nishikawa T, Kobayashi M. The combination of angiogenesis and blood vessel invasion as aprognostic indicator in primary breast cancer. Br J Cancer. 2003;88(12):1900-1908.
  • Lal P, Tan LK, Chen B. Correlation of Her2 status with estrogen and progesterone receptors and histologic features in 3,655 invasive breast carcinomas. Am J Clin Pathol. 2005;123(4):541-546.
  • De Nardo DG, Coussens LM. Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res. 2007;9(4):212.
  • Gottfried E et al. Expression of CD68 in non-myeloid cell types. Scand J Immunol. 2008;67(5):453-463.
  • Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer related inflammation, the seventh hallmark of cancer: Links to genetic instability. Carcinogenesis. 2009;30(7):1073-1081.
  • Galon J et al. Type, density and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;29:1960-1964.
  • Roxburgh CS, McMillan DC. The role of the in situ local inflammatory response in predicting recurrence and survival in patients with primary operable colorectal cancer. Cancer Treat Rev. 2012;38(5):451-66.
  • Mohammed ZM, Going JJ, Edwards J, Elsberger B, McMillan DC. The relationhip between lymphocyte subsets and clinicopathological determinants of survival in patients with primary operable invasive ductal breast cancer. Br J Cancer. 2013;17:1676-84.
  • Al Murri et al. The relationship between the systemic inflammatory response, tumor proliferative activity, T lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer. Br J Cancer. 2008;99(7):1013-1019.
  • Loi S et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase ııı randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy. J Clin Oncol. 2013;31:860-867.
  • Mittendorf E.A et al. PD-L1 Expression in triple-negative breast cancer. Cancer Immunol. 2014;2:361–370.
  • Zhang N et al. Prognostic impact of Tertiary Lymphoid Structures in Breast Cancer Prognosis: A Systematic Review and Meta-Analysis. Cancer Cell Int. 2021;21:536.
  • Sharma P et al. Clinical and biomarker results of neoadjuvant phase II study of pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer (TNBC) (NeoPACT). J Clin Oncol. 2022;40:513.
  • Nederlof I et al. LBA13 nivolumab and ipilimumab in early-stage triple negative breast cancer (TNBC) with tumor-infiltrating lymphocytes (TILs): First results from the BELLINI Trial. Ann Oncol. 2022;33:1382.
  • Loibl S et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022;33:1149–1158.
  • Cardoso F et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:1194–1220.
  • Curigliano G et al. Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the primary therapy of individuals with early creast Cancer. Ann Oncol. 2023;34:970–986.

Meme Karsinomunda Tümörü infiltre eden T Lenfositlerin Yoğunluğunun Prognostik Faktörlerle İlişkisi

Year 2025, Volume: 15 Issue: 2, 118 - 127, 30.06.2025
https://doi.org/10.31832/smj.1625190

Abstract

Giriş: Tümörü infiltre eden lenfositler, tümör mikroçevresindeki immün sistem hücreleridir ve kansere karşı oluşan immün yanıtta kritik rol oynar. Meme karsinomunda, tümörü infiltre eden lenfositlerin miktarının prognostik ve prediktif önemi olabileceği ortaya konmuştur. Çalışmamızda, meme kanserine ait tümör dokularındaki inflamatuar hücreler, TILs Working Group standartları göz önünde bulundurularak değerlendirilmiş ve prognostik faktörler ile ilişkisine bakılmıştır.
Materyal Metod: Sakarya Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı laboratuvarında 2011-2015 yılları arasında incelenen, İnvaziv Karsinom, Özel Tip İçermeyen (NST) tanılı, neoadjuvan kemoterapi almamış 100 hastaya ait mastektomi ve meme koruyucu cerrahi materyalleri çalışmaya dahil edilerek, lenf nodu metastazı, tümör çapı evresi, tümörün histolojik derecesi, östrojen; progesteron ve Her2 reseptörü durumu olmak üzere prognostik parametreleri belirlendi. Tümör bloklarından elde edilen kesitlere CD4(+) ve CD8(+) pozitif lenfositleri tespit etmek için immunohistokimyasal çalışma yapıldı. Belirlenen prognostik parametrelerle inflamatuar hücre yoğunluğu arasındaki ilişki değerlendirildi.
Bulgular: Vakaların 50’sinde lenf nodu metastazı mevcut iken, 50 hastada lenf nodu metastazı yoktu. Hastalara ait prognoz ile ilişkili değişkenlerin alt gruplarından tümörlerin histolojik derecesine göre hasta dağılımına bakıldığında 24 hasta derece 1, 44 hasta derece 2 ve 32 hasta derece 3 idi. Farklı grade ‘lere göre intratümöral stromal CD8 pozitif T lenfosit infiltrasyonu açısından grade 1 ve grade 3 grupları arasında istatistiksel olarak anlamlı pozitif korelasyon görüldü.
Sonuç: Çalışmamıza göre derecesi yüksek tümörlerde CD8(+) T lenfosit infiltrasyonu yoğunluğunun daha fazla olduğu saptanmıştır. Çalışmamız tümörü infiltre eden lenfositlerin yoğunluğundaki artışın prognostik ve prediktif değerinin olabileceği konusunda farkındalık oluşturması açısından önemlidir.

References

  • Ciarka A, Piatek M, Peksa R, Kunc M, Senkus E. Tumor-infiltrating lymphocytes (TILs) in breast cancer: Prognostic and predictive significance across molecular subtypes. Biomedicines. 2024;12:763.
  • Khoury T, Nagrale V, Opyrchal M, Peng X, Wang D, Yao S. Prognostic significance of stromal versus intratumoral infiltrating lymphocytes in different subtypes of breast cancer treated with cytotoxic neoadjuvant chemotherapy. Appl Immunohistochem Mol Morphol. 2018;26:523.
  • Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating Foxp3+ regulatory T cells. Clin Cancer Res. 2008;14:2413–2420.
  • Gu-Trantien C, Loi S, Garaud S, Equeter C, Libin M, De Wind A et al. CD4+ Follicular helper T cell infiltration predicts breast cancer survival. J Clin Investig. 2013;123:2873–2892.
  • Solinas C, Carbognin L, De Silva P, Criscitiello C, Lambertini M. Tumor-infiltrating lymphocytes in breast cancer according to tumor subtype: Current state of the art. Breast. 2017;35:142–150.
  • Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The Evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann. Oncol. 2015;26:259–271.
  • Menard S, Fortis S, Castiglioni F, Agresti R, Balsari A. HER2 as a prognostic factor in breast cancer. Oncology. 2001;2:67–72.
  • Lee AK, De Lellis RA, Silverman ML, Heatley GJ, Wolfe HJ. Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast. J Clin Oncol. 1990;8(9):1457-1465.
  • Gasparini G et al. Tumor microvessel density, p53 expression, tumor size and peritumoral lymphatic vessel invasion are relevant prognostic markers in node negative breast carcinoma. J Clin Oncol.1994;12(3):454-466.
  • Kato T, Kameoka S, Kimura T, Nishikawa T, Kobayashi M. The combination of angiogenesis and blood vessel invasion as aprognostic indicator in primary breast cancer. Br J Cancer. 2003;88(12):1900-1908.
  • Lal P, Tan LK, Chen B. Correlation of Her2 status with estrogen and progesterone receptors and histologic features in 3,655 invasive breast carcinomas. Am J Clin Pathol. 2005;123(4):541-546.
  • De Nardo DG, Coussens LM. Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res. 2007;9(4):212.
  • Gottfried E et al. Expression of CD68 in non-myeloid cell types. Scand J Immunol. 2008;67(5):453-463.
  • Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer related inflammation, the seventh hallmark of cancer: Links to genetic instability. Carcinogenesis. 2009;30(7):1073-1081.
  • Galon J et al. Type, density and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;29:1960-1964.
  • Roxburgh CS, McMillan DC. The role of the in situ local inflammatory response in predicting recurrence and survival in patients with primary operable colorectal cancer. Cancer Treat Rev. 2012;38(5):451-66.
  • Mohammed ZM, Going JJ, Edwards J, Elsberger B, McMillan DC. The relationhip between lymphocyte subsets and clinicopathological determinants of survival in patients with primary operable invasive ductal breast cancer. Br J Cancer. 2013;17:1676-84.
  • Al Murri et al. The relationship between the systemic inflammatory response, tumor proliferative activity, T lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer. Br J Cancer. 2008;99(7):1013-1019.
  • Loi S et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase ııı randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy. J Clin Oncol. 2013;31:860-867.
  • Mittendorf E.A et al. PD-L1 Expression in triple-negative breast cancer. Cancer Immunol. 2014;2:361–370.
  • Zhang N et al. Prognostic impact of Tertiary Lymphoid Structures in Breast Cancer Prognosis: A Systematic Review and Meta-Analysis. Cancer Cell Int. 2021;21:536.
  • Sharma P et al. Clinical and biomarker results of neoadjuvant phase II study of pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer (TNBC) (NeoPACT). J Clin Oncol. 2022;40:513.
  • Nederlof I et al. LBA13 nivolumab and ipilimumab in early-stage triple negative breast cancer (TNBC) with tumor-infiltrating lymphocytes (TILs): First results from the BELLINI Trial. Ann Oncol. 2022;33:1382.
  • Loibl S et al. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022;33:1149–1158.
  • Cardoso F et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:1194–1220.
  • Curigliano G et al. Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the primary therapy of individuals with early creast Cancer. Ann Oncol. 2023;34:970–986.
There are 26 citations in total.

Details

Primary Language Turkish
Subjects Pathology
Journal Section Research Article
Authors

Gözde Çakırsoy Çakar 0000-0001-6851-0945

Mustafa Kösem 0000-0002-2347-0940

Early Pub Date June 12, 2025
Publication Date June 30, 2025
Submission Date January 22, 2025
Acceptance Date April 17, 2025
Published in Issue Year 2025 Volume: 15 Issue: 2

Cite

AMA Çakırsoy Çakar G, Kösem M. Meme Karsinomunda Tümörü infiltre eden T Lenfositlerin Yoğunluğunun Prognostik Faktörlerle İlişkisi. Sakarya Tıp Dergisi. June 2025;15(2):118-127. doi:10.31832/smj.1625190

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