High CD4+/CD8+ Intratumour Ratio is Associated with Favourable Outcome in Triple-negative Breast Cancer

TILs in Breast Cancer
Vol. 17 No. 2 : 2022 (101-124)

Reena RMZThian QZ Reena RMZThian QZ

Abstract
Triple-negative breast cancer (TNBC) is a heterogenous breast cancer subtype which accounts for 10-15% among all diagnosed breast cancers. There is increased resistance of TNBC to conventional chemotherapy and hormonal therapy due to lack of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression. Mutual relationship and interactions between both CD4+ and CD8+ T lymphocytes are very crucial for eliciting adaptive immune system during anti-cancer immune response. This study aimed to determine the ratio of CD4+ and CD8+ T lymphocytes in TNBC by immunohistochemistry assay and to investigate the association of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) with survival outcome. Quantification of both immunostaining TILs subset was done using conventional light microscope. A wide range of CD4+ and CD8+ TILs subset was found within intratumor stroma of TNBC with population mean score of 0.93 and 0.53, respectively. However, the difference of mean population between both TILs subsets was insignificant overall (P-value of CD4+= 0.484; CD8+= 0.835) when compared statistically using independent t-test. The ratio of CD4+/CD8+ in intratumor stroma ranged from 0.50-5.88 among all TNBC subtypes. The high CD4+/CD8+ ratio within intratumor stroma showed favorable association with survival outcome during the 2 years’ follow-up. 
Keywords : CD4+, CD8+, digital pathology, prognostic biomarkers, triple-negative breast cancer (TNBC), tumor-infiltrating lymphocytes (TILs),
Abstrak
Kanser payudara tripel-negatif (TNBC) ialah subjenis kanser payudara yang sangat kompleks dan menyumbang kepada 10-15% daripada semua kanser payudara yang didiagnos. Terdapat peningkatan rintangan TNBC terhadap kemoterapi konvensional dan terapi hormon kerana kekurangan reseptor estrogen (ER), reseptor progesteron (PR) dan ekspresi reseptor faktor pertumbuhan epidermis manusia -2 (HER2). Hubungan dan interaksi antara kedua-dua limfosit T CD4+ dan CD8+ adalah sangat penting untuk merangsang sistem imun adaptif semasa tindak balas imun anti-kanser. Kajian ini bertujuan untuk menentukan nisbah limfosit T CD4+ dan CD8+ dalam TNBC melalui ujian imunohistokimia dan mengkaji hubung kait antara limfosit penyusupan tumor (TIL) CD4+ dan CD8+ dengan kemandirian hidup. Kuantifikasi kedua-dua subset TIL melalui pewarnaan imunohistokimia dilakukan menggunakan mikroskop cahaya konvensional. Pelbagai jenis subset CD4+ dan CD8+ TIL ditemui dalam stroma intratumor TNBC dengan skor min populasi masing-masing antara 0.93 dan 0.53. Walau bagaimanapun, perbezaan purata populasi antara kedua-dua subset TIL adalah tidak signifikan secara keseluruhan (nilai P CD4+ = 0.484; CD8+ = 0.835) apabila dibanding secara statistik menggunakan ujian-t bebas. Nisbah CD4+/CD8+ dalam stroma intratumor adalah berkisar antara 0.50-5.88 di antara semua subspesies TNBC. Nisbah CD4+/CD8+ yang tinggi dalam stroma intratumor menunjukkan hubungan yang baik dengan hasil kemandirian hidup dalam susulan rawatan selama 2 tahun.
Kata Kunci : biomarker prognostik, CD4+, CD8+, kanser payudara tiga kali ganda negatif (TNBC), limfosit penyusupan tumor (TILs), patologi digital,

Correspondance Address
Prof. Dr. Reena Rahayu Md Zin. Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +603-91455359 Email: reenarahayu@ppukm.ukm.edu.my