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Assignee10x Genomics, Inc.
InventorsFlorian Baumgartner, Valeria Giangarra, Sarah Taylor, Yifeng Yin
Estimating the term…
Provided herein are methods for analyzing immune cell infiltration in a cancer stromal region of a biological sample obtained from a subject using machine learning modules. For example, the methods may include (a) identifying a cancerous region or an analyte associated with the cancerous region in the biological sample; (b) identifying a stromal region or an analyte associated with the stromal region in the biological sample; (c) identifying one or more immune cells or an analyte associated with an immune cell in one or more locations in the biological sample; and (d) using (i) the identified cancerous and stromal regions or associated analytes thereof in the biological sample and (ii) the identified one or more immune cells or associated analytes thereof to analyze immune cell infiltration in the cancer stromal region of the biological sample obtained from the subject.
A method of analyzing immune cell infiltration in a cancer stromal region of a biological sample, the method comprising:
The method of any one of the preceding claims, wherein the cancerous region comprises one or more of a benign tumor, a pre-metastatic tumor, a malignant tumor, and one or more inflammatory cells.
The method of any one of the preceding claims, wherein the stromal region comprises one or more of connective tissue, blood vessels, and inflammatory cells.
The method as in any one of the preceding claims, further comprising permeabilizing the biological sample.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region, an analyte associated with the stromal region, and/or an analyte associated with an immune cell is a nucleic acid.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region, the analyte associated with the stromal region, and/or the analyte associated with an immune cell is detected by the steps comprising:
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region, the analyte associated with the stromal region, and/or the analyte associated with an immune cell is detected using in situ sequencing.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region, the analyte associated with the stromal region, and/or the analyte associated with an immune cell is detected using an antibody.
The method of any one of one of the preceding claims, further comprising contacting the biological sample with one or more stains.
The method of any one of the preceding claims, wherein the analysis of immune cell infiltration in the cancer stromal region of the biological sample comprises determining abundance of immune cells in the cancer stromal region in the biological sample.
The method of any one of the preceding claims, wherein the determining comprises:
The method of any one of the preceding claims, wherein the identification of the one or more immune cells comprises segmenting immune cells from the image data.
The method of one of the preceding claims, further comprising determining a cancer prognosis based on the immune infiltration.
The method of one of the preceding claims, further comprising scoring or determining the severity of the cancer in the subject based on the immune infiltration score.
The method of one of the preceding claims, wherein the determining comprises identifying the ratio of one or more tumor infiltrating lymphocytes (TILs) to one or more tumor infiltrating B cells (TIBs) or one or more tumor infiltrating T cells to one or more tumor infiltrating B cells (TIBs).
The method of one of the preceding claims, further comprising administering a therapeutic treatment, wherein the therapeutic treatment comprises surgery, chemotherapeutic agents, growth inhibitory agents, cytotoxic agents, agents used in radiation therapy, anti-angiogenesis agents, cancer immunotherapeutic agents, apoptotic agents, antitubulin agents, or a combination thereof.
The method as in any one of the preceding claims, wherein the biological sample is obtained from a biopsy from a subject.
The method as in any one of the preceding claims, wherein the biological sample is obtained from a surgical excision from a subject.
The method as in any one of the preceding claims, wherein the biological sample is a tissue section.
The method as in any one of the preceding claims, wherein the biological sample is a tissue section on a slide.
The method as in any one of the preceding claims, wherein the biological sample is a formalin-fixed, paraffin-embedded (FFPE) sample, a frozen sample, or a fresh sample.
The method as in any one of the preceding claims, wherein the biological sample is an FFPE sample.
The method of any one of the preceding claims, wherein the immune cells are selected from a B cell, a T cell, an NK cell, a monocyte, a macrophage, a neutrophil, a granulocyte, an innate lymphoid cell, or a dendritic cell or combinations thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is selected from an analyte from the AKT pathway, an analyte from the JAK-STAT pathway, and an analyte from the Notch pathway or combinations thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is selected from SCGB2A1, MKI67, BRCA1, BRCA2, PIKCD, CALML6, MYC, TP53, PALB2, RAD51, and MSH2 or combinations thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is selected from SCGB2A1, MKI67, BRCA1, BRCA2, PIK3CD, and CALML6 or combinations thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is selected from PRKCI, VTCN1, MECOM, TOP2A, SHDH, XPO1, TFRC, FUT8, SOX17, PBX1, EIF42, WTT, byproducts, precursors, and degradation products thereof, and any combination thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is selected from VTCN1, MECOM, TOP2A, XPO1, FUT8, SOX17, PBX1, EIF42, WTT, byproducts, precursors, and degradation products thereof, and any combination thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is TOP2A, and byproducts, precursors, and degradation products thereof.
The method of any one of the preceding claims, wherein the analyte associated with the cancerous region is XPO1, and byproducts, precursors, and degradation products thereof.
The method of any one of the preceding claims, wherein the analyte associated with the stromal region is selected from VIM, EPCAM, FAP, and CDH1.
The method of any one of the preceding claims, wherein the analyte associated with the stromal region is selected from FAP, VCAN, ACTA2, and PDGFRB.
The method of any one of the preceding claims, wherein the analyte associated with an immune cell is selected from BLK, CD19, FCRL2, MS4A1, KIAA0125, TNFRSF17, TCL1A, SPIB, PNOC, PTRPC, PRF1, GZMA, GZMB, NKG7, GZMH, KLRK1, KLRB1, KLRD1, CTSW, GNLY, CCL13, CD209, HSD11B1, LAG3, CD244, EOMES, PTGER4, CD68, CD84, CD163, MS4A4A, TPSB2, TPSAB1, CPA3, MS4A2, HDC, FPR1, SIGLEC5, CSF3R, FCAR, FCGR3B, CEACAM3, S100A12, KIR2DL3, KIR3DL1, KIR3DL2, IL21R, XCL1, XCL2, NCR1, CD6, CD3D, CD3E, SH2D1A, TRAT1, CD3G, TBX21, FOXP3, CD8A, CD8B, CD79A, CD79B, CD4, IGHA1, IGHG2, JCHAIN, IGKC, CD27, CD38, CD16, IL17RB, FANK1, CTLA4, MSR1, MRC1, NKG7, FCN1, TIGIT/LAG3.
The method as in any one of the preceding claims, wherein the one or more immune cells is selected from:
The method of any one of the preceding claims, wherein the immune infiltrating cells is a tumor infiltrating B cell (TIB).
A method of determining immune cell infiltration in a biological sample comprising one or more cancerous regions and one or more stromal regions in a subject, the method comprising:
A method of determining immune cell infiltration in a biological sample comprising one or more cancerous regions and one or more stromal regions, the method comprising:
A computer implemented method comprising:
A system comprising:
Dependencies are inferred from the claim text.