Methods of using PD-L1 expression in treatment decisions for cancer therapy
Methods of using detection of PD-L1 expression by circulating cancer cells in the screening, monitoring, treatment and diagnosis of cancer in subjects are disclosed. The methods are based on assaying one or more of circulating tumor cells (CTCs), epithelial to mesenchymal transition CTCs (EMTCTCs), cancer associated macrophage-like cells (CAMLs), and cancer associated vascular endothelial cells (CAVEs) isolated from a subject having cancer for PD-L1 expression.
1. A method of treating a subject having cancer, comprising:
(a) assaying circulating tumor cells (CTCs) and cancer associated macrophage-like cells (CAMLs), and optionally one or more of epithelial to mesenchymal transition CTCs (EMTCTCs) and cancer associated vascular endothelial cells (CAVEs), isolated from a subject having cancer for PD-L1 expression, and
(b) administering a therapeutically effective amount of an immune checkpoint inhibitor to the subject when PD-L1 expression is detected,
wherein the immune checkpoint inhibitor is one or more of Nivolumab, Ipilimumab, Pembrolizumab, Atezolizumab, Tremelimumab, and Durvalumab.
2. The method of claim 1 , further comprising administering a therapeutically effective amount of one or more additional anti-cancer agents to the subject.
3. The method of claim 2 , wherein the one or more additional anti-cancer agents are selected from the group consisting of immunotherapeutic agents, chemotherapeutic agents, radiotherapeutic agents, existing cancer drugs, CCR5 and CXCR4.
4. The method of claim 2 , wherein the one or more additional anti-cancer agents are selected from the group consisting of T-VEC, AM-0010, CXCR4 antagonist, TGF-beta kinase inhibitor galunisertib, anti-CSF-1R monoclonal antibody, Abemaciclib, Faslodex, necitumumab, AZD9291, ramucirumab, TPIV 200, Galunisertib, cancer vaccines, cytokines, cell-based therapies, bi- and multi-specific antibodies, tumor-2 targeting mAbs, Rituximab, oncolytic viruses, reovirus, Blinatumomab, Sipuleucel-T, T-Vec, IL-2, IFN-a, Trastuzumab, Celuximab, bevacizumab, Tim-3, BTLA, anti-IL-10, GM-CSF, anti-angiogenesis treatment, VEGF blockade, HMGB1, NrpI, TAM receptor tyrosine kinases, Axl, MerTK, ALT-803, IL-15, Immunosuppressive Ligand Phosphatidylserine (PS), bavituximab, bevacizumab (anti-VEGF), coblmetinib (MEK inhibitor), vemurafenib (BRAF inhibitor), erlotinib (EGFR), alectinib (ALK inhibitor), bevacizumab (anti-VEGF), pazopanib (tyrosine kinase inhibitor), dabrafenib (BRAF inhibitor), trametinib (MEK inhibitor), durvalumab (anti-PD-L1), sunitinib (RTK inhibitor), pazopanib (RTK inhibitor), sargramostim, VISTA, TIM-3, LAG-3, PRS-343, CD137 (4-1 BB)/HER2 bispecific, USP7, anti-HER2, SEMA4D, CTLA-4, PD-i, PD-L1, and PD-L2.
5. The method of claim 1 , wherein the assaying for PD-L1 expression is by one or more of detecting PD-L1 protein expression and detecting PD-L1 mRNA production.
6. The method of claim 5 , wherein the PD-L1 protein expression is detected via immunohistochemistry (IHC).
7. The method of claim 6 , wherein IHC is performed using an anti-PD-L1 antibody.
8. The method of claim 6 , wherein IHC is performed using immunofluorescence (IF) staining, wherein one or more antibodies with binding specificity for PD-L1 are utilized.
9. The method of claim 8 , wherein binding of the anti-PD-L1 antibody to PD-L1 is detected via a fluorescent compound conjugated to the anti-PD-L1 antibody or via a fluorophore-conjugated secondary antibody with binding specificity for the anti-PD-L1 antibody.
10. The method of claim 1 , wherein PD-L1 expression is detected when the level of PD-L1 expression is greater than PD-L1 expression in a population of stromal cells from a subject of the same species that does not have cancer.
11. The method of claim 1 , wherein CTCs, EMTCTCs, CAMLs, and CAVEs are isolated from a bodily fluid obtained from the subject having cancer.
12. The method of claim 1 , wherein the cancer is a solid tumor.
13. The method of claim 12 , wherein the solid tumor is a carcinoma, sarcoma, neuroblastoma or melanoma.
14. The method of claim 1 , wherein the cancer is lung cancer, breast cancer, prostate cancer, pancreatic cancer, melanoma, bladder cancer, kidney cancer, head and neck cancer, colorectal cancer, liver cancer, ovarian cancer, neuroblastoma, sarcoma, osteosarcoma, esophageal, brain & ONS, larynx, bronchus, oral cavity and pharynx, stomach, testis, thyroid, uterine cervix, or uterine corpus cancer.
15. The method of claim 1 , wherein at least one CTC, EMT cell, CAML, or CAVE exhibits at least one RAD50 foci after radiation treatment.
16. The method of claim 11 , wherein the bodily fluid is blood.
17. The method of claim 11 , wherein the cells are isolated from the bodily fluid via a microfiltration assay using a low-pressure vacuum system.