Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

Abstract

Asian Pac J Cancer Prev, 15 (8), 3757-3761 IntroductionBreast cancer is the most common cause of cancer death in women worldwide (Key et al., 2001), and represents the leading or second most leading cancer in females in India (Ferlay et al., 2010;D'Souza et al., 2013a;2013b). Currently, two major challenges of breast cancer research are; to understand the interrelation between breast cancer and anti-tumor immunity, and to identify candidates whose targeting would contribute to enhance anti-tumor efficiency (Mamessier et al., 2012).The cancer tissue is invaded by a mixed population of immune cells, including T-cells, B-cells, natural killer (NK) cells and macrophages. For a long time NK cells were considered merely as relatively primitive killers, but now they are seen not only as bonafide actors in innate immunity but are also important cells that shape and influence the adaptive immune responses (Poli et al., 2009). NK cells are effector lymphocytes of innate immune system that act by limiting the growth and dissemination of the tumor and are known to have an immunoregulatory role.An established marker for NK cells, CD56, is an AbstractPurpose: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. Material and Methods: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. Results: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (χ 2 =4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (χ 2 =1.60, p>0.05). Conclusion: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.

Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma

“…These results suggested that MCT4‐induced NK cell activation and acidosis of the tumor microenvironment are regulated by an MCT4‐dependent lactate flux in the 4T1 cell line. In addition, we discovered by IHC that the activities of the NK cells also decreased in mouse breast cancer tissues, and this finding is consistent with a previous report . Based on the principles outlined in the Reverse Warburg Effect hypothesis, glycolysis and lactate can be conducive to the growth of tumor cells .…”

“…In addition, we discovered by IHC that the activities of the NK cells also decreased in mouse breast cancer tissues, and this finding is consistent with a previous report. 36 Based on the principles outlined in the Reverse Warburg Effect hypothesis, glycolysis and lactate can be conducive to the growth of tumor cells. [37][38][39] It has been previously established that the antitumor activities of NK cells are impaired by hypoxia, acidosis, and glucose metabolic abnormalities.…”

“…C, The pH values were measured using pH meters every 2 h and analyzed by Wilcoxon's test for the control and 7acc1 (0.1 mmol/L)-treated groups. D, The pH values were described at different incubation time points (24,36, and 72 h) and different interference ShMCT4 vectors (weak "1," medium "2," and strong "3") in 4T1-ShMCT4 and 4T1-Shcontrol groups. After this shift, the culture supernatant pH value increased by 0.1 to 0.4 pH units; these results were consistent and repeatable among biological replicates.…”

The immune system and cancer evasion strategies: therapeutic concepts

“…There is evidence that these altered NK cells directly reduce the number of T cells in the tumour microenvironment, thus also inhibiting the immune response to tumours . The notion of a possible tumour‐promoting function of NK cells is supported by the finding of an association between increased NK‐cell infiltration and poorer outcome in metastatic ovarian carcinoma and invasive ductal carcinoma of the breast .…”

When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer

“…Under the influence of cytokines and chemokines secreted by the cancer cells, fibroblasts phenotypically change into cancer-associated fibroblasts (CAFs), macrophages are activated and attracted toward the tumor environment (tumor-associated macrophages [TAMs]), and lymphocytes infiltrate the tumor (tumor-infiltrating lymphocytes [TILs]). These CAFs, TAMs, and TILs exert tumor-stimulating or tumor-protective actions, are involved in therapy resistance, and are linked with breast cancer prognosis [4][5][6][7][8][9][10][11][12].…”