Methods of treating endometriosis

A method of treating a subject in need thereof, comprising:

• administering one or more of a CD20 inhibitor, an IL17 inhibitor, an anti-inflammatory agent, and optionally further administering a programmed cell death protein 1 (PD1) inhibitor, a cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitor, a T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) inhibitor, a lymphocyte activation gene 3 (LAG3) inhibitor, a CD86 inhibitor, a nectin-2 inhibitor, a macrophage migration inhibitory factor (MIF) inhibitor, and a tumor necrosis factor (TNF) inhibitor, to a subject indicated as having endometrioma,
• wherein the subject is detected in a biological sample comprising endometrial-type tissue, according to a method of claim 15, with:
• the higher number of exhausted CD8 T-cells and/or higher number of plasma cells, per unit tissue size, compared to that in a specimen of peritoneal endometriosis, eutopic endometrium, or uninvolved ovary, and the lower number of lymphoid aggregates and/or lower number of B cells, per unit tissue size, compared to the specimen of peritoneal endometriosis, eutopic endometrium, or uninvolved ovary, and/or
• wherein the subject is detected with presence of endometrioma in ovary optionally via laparoscopy, ultrasound, or magnetic resonance imaging (MRI).

A method of treating a subject in need thereof, comprising:

• administering an endometriosis therapy to a subject detected according to the method of claim 16 with:
• the higher number of myeloid cells and/or higher number of B cells, per unit tissue size in a biological sample of the subject, compared to respective number per unit tissue size in a specimen of eutopic endometrium, or unaffected ovary, and/or
• the higher expression level in macrophages of all or one or two of insulin like growth factor 1 (IGF1), embigin (EMB), and transforming growth factor beta-1 (TGFB1) and/or a higher expression level in B cells of MS4A1, CD79A, or both, compared to the specimen of eutopic endometrium, or unaffected ovary,
• wherein the endometriosis therapy comprises one or more of a CD20 inhibitor, an IL17 inhibitor, an anti-inflammatory agent, a therapy to down-regulate central memory T cells, Th17 T-cells, natural killer cells, B-cells, effector memory T-cells, exhausted T-cells, and/or M2 macrophages, an antihistamine, and/or a therapy to down-regulate, mast cells, M1 macrophages, plasma cells, and/or activated T-cells;
• or the endometriosis therapy comprises a procedure to remove endometriosis tissue;
• wherein the myeloid cells comprise mast cells, macrophages, or both.

A method of detecting endometrioma in a subject, comprising:

• detecting, in a biological sample comprising endometrial tissue of the subject:
• a higher number of exhausted CD8 T-cells and/or a higher number of plasma cells, per unit tissue size, compared to respective number of a reference subject with peritoneal endometriosis in the absence of endometrioma, a reference subject with eutopic endometrium, or an uninvolved ovary tissue of the subject or of either reference subject,
• a lower number of lymphoid aggregates and/or a lower number of B cells, per unit tissue size, compared to that of the reference subject with peritoneal endometriosis in the absence of endometrioma, and/or
• a lower number of myeloid cells, per unit tissue size, than that of the reference subject with peritoneal endometriosis in the absence of endometrioma, optionally the number of the myeloid cells being higher compared to that of the reference subject with eutopic endometrium or compared to the uninvolved ovary tissue;
• and optionally:
• wherein the exhausted CD8 T-cells are positive for all or one or more of PD-1, CTLA4, TIGIT, VISTA, and LAG3, and optionally negative for TIM3,
• wherein macrophages in the biological sample are in the M2 state or are positive for all or one or more of IL10, VSIG4, RGS1, LYVE1, THBS1,and HBEGF, and/or
• wherein B-cells in the biological sample have a lower expression level of MS4A1, CD79A, or both, compared to B-cells of a subject with peritoneal endometriosis but not endometrioma or a subject with eutopic endometrium.

A method of detecting peritoneal endometriosis in a subject, comprising:

• detecting, in a biological sample comprising endometrial tissue of the subject:
• a higher number of myeloid cells and/or a higher number of B cells, per unit tissue size, compared to respective number per unit tissue size in a reference subject with endometrioma, a reference subject with eutopic endometrium, or an uninvolved ovary tissue of the subject or of either reference subject,
• a higher number of lymphoid aggregates, per unit tissue size, compared to that of the reference subject with endometrioma, and/or
• a higher expression level in macrophages of all or one or two of IGF1, EMB, and TGFB1 and/or a higher expression level in B cells of MS4A1, CD79A, or both, compared to that in the reference subject with endometrioma,
• wherein the subject does not have or is not detected with endometrioma.

A method of classifying or staging endometriosis in a subject in need thereof, comprising:

• obtaining a biological sample comprising biopsy of a tissue with suspected endometriosis or of an endometrial tissue of the subject, and
• measuring in the biological sample one or more of:
• a number of exhausted CD8 T-cells,
• a number of plasma cells and/or a number of B-cells,
• a number of myeloid cells, and
• a number of lymphoid aggregates,
• wherein a higher number of the exhausted CD8 T-cells, a higher number of the plasma cells, a lower number of the B-cells, a lower number of the myeloid cells, and a lower number of the lymphoid aggregates, per unit tissue size, compared to respective numbers in a reference subject with peritoneal endometriosis but not endometrioma. indicates that the subject has endometrioma or that the endometriosis is at an endometrioma stage, and wherein a lower number of the exhausted CD8 T-cells, a lower number of the plasma cells, a higher number of the B cells, a higher number of the myeloid cells, and a higher number of the lymphoid aggregates, per unit tissue size, compared to respective numbers in a reference subject with endometrioma, indicates that the subject has peritoneal endometriosis but not endometrioma or that the endometriosis is at a peritoneal stage.