Immunotherapy markers
The present invention relates to the identification and use of markers indicative for the response of a subject to immunotherapy as anti-cancer treatment. The markers are particularly useful in predicting response of a subject to immunotherapy with PD-1 or PD-L1 antagonists in the treatment of cancer. PD-1 and PD-L1 antagonists are typically used as immunotherapy in the treatment of several types of cancer, including melanoma, non-small cell lung cancer (NSCLC), and squamous cell carcinoma.
1 . A method of treating a subject with non-small cell lung cancer, the method comprising:
determining whether a cancer sample from the subject comprises one or more antimicrobial peptides selected from the group consisting of neutrophil defensin 1, neutrophil defensin 2 and neutrophil defensin 3; and
administering to the subject an effective amount of a PD-1/PD-L1 antagonist when one or more of the antimicrobial peptides are present within the cancer sample.
2 . The method of claim 1 , wherein the PD-1/PD-L1 antagonist is selected from the group consisting of Pembrolizumab, Nivolumab and/or Atezolizumab.
3 . The method of claim 1 , wherein determining whether the cancer sample comprises one or more antimicrobial peptides comprises analyzing the cancer sample using MALDI-MSI.
4 . The method of claim 1 , wherein determining whether the cancer sample comprises one or more antimicrobial peptides comprises analyzing the cancer sample using immunohistochemistry.
5 . The method of claim 4 , wherein analyzing the cancer sample using immunohistochemistry comprises using one or more biomarker-specific antibodies.
6 . The method of claim 5 , wherein the one or more biomarker-specific antibodies is selected from the group consisting of antibodies against neutrophil defensin 1, antibodies against neutrophil defensin 2 and antibodies against neutrophil defensin 3.
7 . The method of claim 1 , wherein the cancer sample is a tissue biopsy section.
8 . The method of claim 7 , wherein the tissue biopsy section comprises formalin-fixed paraffin-embedded tissue biopsy sections.
9 . The method of claim 7 , wherein the tissue biopsy section comprises fresh frozen tissue biopsy sections.
10 . A method of diagnosing and treating a subject with a non-small cell lung cancer likely to respond to an immunotherapy, the method comprising:
obtaining a cancer sample from the subject;
detecting whether one or more antimicrobial peptides selected from the group consisting of neutrophil defensin 1, neutrophil defensin 2, and neutrophil defensin 3 is present in the sample by immunohistochemistry or MALDI-MSI;
diagnosing the subject with a cancer likely to respond to the immunotherapy comprising a PD-1/PD-L1 antagonist when the presence of one or more antimicrobial peptides is detected; and
administering an effective amount of the immunotherapy comprising the PD-1/PD-L1 antagonist to the diagnosed subject.
11 . The method of claim 10 , further comprising detecting whether neutrophil defensin 1, neutrophil defensin 2, and neutrophil defensin 3 are present in the cancer sample.
12 . The method of claim 10 , wherein the PD-1/PD-L1 antagonist is selected from the group consisting of Pembrolizumab, Nivolumab and/or Atezolizumab.