Impact of Pattern Recognition Receptors on the Prognosis of Breast Cancer Patients Undergoing Adjuvant Chemotherapy

Abstract

Pattern recognition receptors allow the innate immune system to perceive the presence of microbial products and to launch the first steps of the defense response. Some pattern recognition receptors also sense endogenous ligands that are released from uninfected dying cells, thereby activating immune responses against dead-cell antigens. This applies to toll-like receptors 3 and 4 (TLR3, TLR4), which sense doublestranded RNA and high-mobility group protein B1 (HMGB1), respectively, as well as to formyl peptide receptor-1 (FPR1), which interacts with Annexin A1 (ANXA1) from dead cells. Breast cancer patients who bear loss-of-function alleles in TLR3, TLR4, and FPR1 exhibit a reduced metastasis-free and overall survival after treatment with anthracycline-based adjuvant chemotherapy. These genetic defects are epistatic with respect to each other, suggesting that they act on the same pathway, linking chemotherapy to a therapeutically relevant anticancer immune response. Loss-of-function alleles in TLR4 and FPR1 also affect the prognosis of colorectal cancer patients treated with oxaliplatin-based chemotherapy. Altogether, these results support the idea that conventional anticancer treatments rely on stimulation of anticancer immune responses to become fully efficient. Cancer Res; 76(11); 3122-6. Ó2016 AACR.

TLR4 Promotes Breast Cancer Metastasis via Akt/GSK3β/β‐Catenin Pathway upon LPS Stimulation

“…In addition, TLR4 plays an important role in increasing the efficiency of conventional anticancer treatment. Loss-of-function alleles in TLR4 has been shown to affect metastasis-free survival and overall survival rates after treatment with anthracycline-based adjuvant chemotherapy in breast cancer patients (Vacchelli et al, 2016). Moreover, TLR4 has also been shown to promote metastasis in nonsmall cell lung cancer (Liu et al, 2015b), hepatocellular carcinoma (Liu et al, 2015a), oral squamous cell carcinoma (He et al, 2015), breast cancer (Yang et al, 2014), and colon cancer (Santaolalla et al, 2013).…”

Lurbinectedin synergizes with immune checkpoint blockade to generate anticancer immunity

“…Loss-of-function mutations of FPR1, P2RX7 or TLR4 in breast cancer are negatively correlated with clinical response to adjuvant chemotherapy with anthracyclines. 3,10,13,14,[17][18][19] These results imply the obligate contribution of anticancer immune responses to the success of ICD-inducing chemotherapies.…”

Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity

“…[112] Loss-of-function mutations of FRP1 in cancer patients (namely cancer and colon cancers) have been correlated with shorter metastasis-free and overall survival after treatment with anthracyclines-inducing ICD. [113] ICD was initially thought to be triggered by a small set of chemotherapeutics agents (e.g., doxorubicin, mitoxantrone, oxaliplatin, bortezomib, etc) [104]. Unfortunately, most of the drugs used in chemotherapy (e.g., cisplatin, etoposide, mitomycin C) are unable to induce ICD, meaning that cancer cell destruction is caused in a way that is ineffective regarding immune recognition [114,115].…”