Tumor-infiltrating lymphocytes (TILs) have emerged as an important aspect of the immune response within the tumor microenvironment, especially in the context of the triple-negative breast cancer (TNBC) subtype. TILs interact with various cells, shaping a unique microenvironment that affects.

disease progression and treatment outcomes [1]. The number of TILs presents within the tumor has been identified as a critical factor affecting patient prognosis, survival rates, and response to treatment [2,4,5]. TNBC has a higher TIL count compared to other subtypes. Denkert et al.'s study [6], along with other studies [3,4], indicates that elevated TIL levels are linked to a reduced risk of recurrence and extended disease-free survival.

In 2014, the International TILs Working Group, a global collaboration involving universities and hospitals, introduced a standardized method for evaluating TILs on H&E slides to ensure consistency in evaluation [7].Assessment of PD-L1 levels can be performed using visual histologic intensity scores, and correlating these scores with results from digital image analysis showed a strong and consistent correlation.

However, limitations in the reporting format persist. A key issue is the absence of clear guidelines for reporting TILs quantity, such as percentage range, low-intermediate-high categories, along with a lack of defined threshold values. Unlike hormonal status tests, the ambiguity in reporting TILs parameters undermines the utility of investing time in TILs assessment in pathology reports for guiding patient treatment decisions.

In TNBC, PD-L1 expression, alongside TILs, plays a complex role in shaping the tumor microenvironment [12,13,[16], [17], [18]]. Tumors with PD-L1 expression often exhibit a higher presence of PD-L1-positive lymphocytes, which frequently aligns with higher TILs levels, impacting clinical outcomes, leading to a more favorable prognosis, and influencing treatment response [10,13,16,17,19,25]. This expression is attributed to oncogenic processes within the tumor or elevated interferon-γ production by TILs, which acts as a negative immune regulator, enhancing tumor PD-L1 expression. As a result, even when there's a high number of immune cells, they might not effectively eliminate tumor cells due to the persistent PD-L1 expression. PD-L1 inhibitors, such as Pembrolizumab (KEYTRUDA) and Atezolizumab (TECENTRIQ), along with specific PD-L1 immunohistochemistry companion clones like 22C3 and SP142, have shown significant survival benefits in TNBC patients in clinical trials [23,24,33]. To this end, we determined the TILs threshold in TNBC that indicates a strong likelihood of PD-L1 expression. By pinpointing this optimal cut-off, which implies substantial PD-L1 expression, TILs surpassing this threshold not only acts as a positive predictive indicator for the patient but also guides clinicians on when a PD-L1 immunohistochemical study might be warranted for that case.