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Table 2 Exemplary literature for all markers included in the predictive score model. Negatively associated markers are typed in red and positive categorized markers in green

From: Breast cancer scoring based on a multiplexed profiling of soluble and cell-associated (immune) markers facilitates the prediction of pembrolizumab therapy

Biomarker

Prognostic/predictive value and references

mMHC-I

• MHC-I loss associated with a lack of response to immunotherapy [19, 20]

TILs

• Pos. prognostic factor in TNBC [21, 22]

• Predictive in atezolizumab [23] and pembrolizumab [24] treated mTNBC

mPD-1

• Pos. prognostic factor for survival in many cancer subtypes including BC [25]

mCD137

• Costimulatory receptor expressed on activated T lymphocytes, dendritic cells (DCs), and NK cells [26]

• Predictive for pembrolizumab treated HNSCC patients [28]

CM/EM T cells

• High numbers of CD45RO+ memory T cells within different primary malignancies [29] including TNBC [30] are associated with favourable clinical outcome.

CD8 in TIL

• Higher CD3+ infiltration [31] as well as CD8+ infiltration [32] associated with increased pCR in BC patients receiving NAT

• Positive predictive for immunotherapy response in different cancers [33,34,35] including BC [35, 36]

• Predictive for improved progression free survival (PFS) and OS after treatment with atezolizumab in TNBC [37]

mPD-L1 on myeloid cells

• Associated with good clinical outcome in BC [38, 40]

• Predictive for response to neoadjuvant Durvalumab treatment in TNBC [41]

LAG-3+ TIL

• Associated with better OS in different types of cancers [14] also in TNBC [13, 42] and ER- [42, 43]

TIM-3+ TIL

• Independent favorable prognostic factor in BC [11, 44,45,46]

• Increased levels associated with improved survival in BC treated with chemotherapy [47]

sLAG-3

• Prognostic (OS, PFS) in mHR+ [48]

• High concentration before ICI in solid cancer significantly impaired PFS and OS [51]

MHC II

• High MHC-II expression associated with positive responses to IC therapy in melanoma [52, 53] [54] and in HER2- BC [55].

• Associated with an improved prognosis in TNBC [56,57,58,59]

CD24

• Associated with poor prognosis, tumor size and lymph node positivity in BC [60]

mPD-L1 (tumoral)

• Associated with a worse OS in BC [61]

sPD-1

• Associated with advanced disease and worse outcome [62]

• High levels have been associated with poor cytotoxic therapy response in TNBC [63]

sPD-L1

• More likely to develop progressive disease upon ICI treatment in different solid tumors [64], specifically in lung [65] and melanoma patients [66, 67].

sPD-L2

• Higher sPD-L2 levels in patients with Ki67 > 30% and in tumor grade III-IV BC patients [68].

sCD25

• Negative prognostic marker in HNSCC [70, 71], lung [72], and multiple myeloma [73] patients.

• Lack of long term benefit of ICI in lung [72] and association with resistance to CTLA-4 blockade in melanoma [74]

sCD27

• Negative prognostic factor associated with reduced survival in lung cancer [75], HNSCC [70], and diffuse large B-cell lymphoma [76]

• Negative prognostic marker in solid cancer patients undergoing ICI [51]

sTIM-3

• Associated with advanced NSCLC disease [77] or increased invasion [78], and anti-PD-1 resistance [79]

• Low sTIM-3 level correlated to increased response to anti-PD-1 treatment [80] in NSCLC patients

Gal-9

• Soluble immunosuppressive agents in various malignancies [81, 82].

CD33 in PB

• High pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates to neoadj. Chemotherapy in TNBC [83].

PD-L1 on B cells

• PD-L1 expression on B cells pursue significant immunosuppressive effect in various tumors [86]