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Comprising major components of the TME, exploiting tumor-associated inflammation has long been sought for therapeutic purposes. Our group identified inflammatory responses in breast cancer cells that elicit sensitivity to oxidative stressors, namely the complex I inhibitor, phenformin. In our immune-competent murine breast cancer models, sensitivity to phenformin was modest. However, sensitivity was largely improved when combined with TLR3/4 agonists \(the dsRNA-mimic, poly I:C; or the synthetic lipid A analog, CRX527\). Given the large role of the innate immune system in the generation of this pathogen-associated inflammation, we analyzed systemic and tumor-infiltrating leukocyte diversity in our models by single-cell RNA-sequencing and flow cytometry. Combination therapy induced the expansion of specific CD11b+ Ly6G+ neutrophil populations in the blood and the TME. Using high-throughput proteomics, we highlight differential granule production and frequency which correlates with increased ROS production in cancer cells and synergizes with complex I inhibitors. The granulocyte-dependent tumoricidal synergy between oxidative stress and inflammation has not yet been described, establishing these findings as novel additions to the field of tumor-immune biology.) /Pg 7 0 R /K [17] >> endobj 27 0 obj << /Type /StructElem /S /H3 /T (FRIDAY) /E (FRIDAY) /Pg 7 0 R /K [0] >> endobj 28 0 obj << /Type /StructElem /S /H3 /T (TIME) /E (TIME) /Pg 7 0 R /K [2] >> endobj 29 0 obj << /Type /StructElem /S /H6 /T (9 February 2024) /E (9 February 2024) /Pg 7 0 R /K [1] >> endobj 30 0 obj << /Type /StructElem /S /H6 /T (09:00-10:00 am) /E (09:00-10:00 am) /Pg 7 0 R /K [3] >> endobj 31 0 obj << /Type /StructElem /S /H4 /T (Zoom Meeting ID: 814 254 6865) /E (Zoom Meeting ID: 814 254 6865) /Pg 7 0 R /K [7] >> endobj 32 0 obj << /Type /StructElem /S /P /ActualText (For more information: ) /Pg 7 0 R /K [13] >> endobj 33 0 obj << /Type /StructElem /S /P /ActualText (Aiten Ismailova | aiten.ismailova@mail.mcgill.ca) /Pg 7 0 R /K [14] >> endobj 34 0 obj << /ca 1 /BM /Normal >> endobj 35 0 obj << /CA 1 /ca 1 /LC 0 /LJ 0 /LW 7 /ML 4 /SA true /BM /Normal >> endobj 36 0 obj << /Type /Font /Subtype /Type0 /BaseFont /AAAAAA+Garet-Bold /Encoding /Identity-H /DescendantFonts [40 0 R] /ToUnicode 41 0 R >> endobj 37 0 obj << /Type /Font /Subtype /Type0 /BaseFont /BAAAAA+CanvaSans-Regular /Encoding /Identity-H /DescendantFonts [42 0 R] /ToUnicode 43 0 R >> endobj 38 0 obj << /Type /Font /Subtype /Type0 /BaseFont /CAAAAA+CanvaSans-BoldItalic /Encoding /Identity-H /DescendantFonts [44 0 R] /ToUnicode 45 0 R >> endobj 39 0 obj << /Type /Font /Subtype /Type0 /BaseFont /DAAAAA+CanvaSans-Bold /Encoding /Identity-H /DescendantFonts [46 0 R] /ToUnicode 47 0 R >> endobj 40 0 obj << /Type /Font /FontDescriptor 48 0 R /BaseFont /AAAAAA+Garet-Bold /Subtype /CIDFontType2 /CIDToGIDMap /Identity /CIDSystemInfo 49 0 R /W [0 [846 0 235 730] 16 [689 807] 23 [772 0 0 0 606] 37 [567 816] 44 [760 0 0 327] 63 [576] 69 [934 770] 88 [665] 91 [704 0 0 0 641] 103 [663] 108 [740] 126 [692] 730 [575] ] /DW 833 >> endobj 41 0 obj << /Length 330 /Filter /FlateDecode >> stream x]Mn0>"LR !%XG=R1! n_3CTK<:W֌aK5km]Ä U6%) 3eG. b1˝9u>4 _ vk>&׻Y5?' endstream endobj 42 0 obj << /Type /Font /FontDescriptor 50 0 R /BaseFont /BAAAAA+CanvaSans-Regular /Subtype /CIDFontType2 /CIDToGIDMap /Identity /CIDSystemInfo 51 0 R /W [0 [715.82031 245.11719 670.89844] 21 [758.78906] 35 [565.91797 742.1875] 44 [300.29297] 55 [553.22266 0 0 0 565.91797] 65 [903.80859 761.23047] 83 [650.87891 0 783.20313 661.13281 0 0 0 611.81641] 97 [583.00781] 102 [735.83984] 119 [633.78906] 125 [566.89453] 130 [557.12891] 142 [642.57813 555.17578] 149 [643.06641 0 0 0 574.21875] 163 [383.78906 551.75781] 169 [620.11719 0 0 267.08984] 190 [292.96875] 196 [917.96875 620.11719] 203 [618.16406] 214 [642.57813 0 643.06641 416.01563 0 0 0 498.04688] 228 [410.15625] 233 [611.81641] 244 [570.80078 785.15625] 250 [501.95313 567.87109] 276 [702.14844 532.22656 548.82813 0 604.98047 590.82031 643.06641 0 604.00391 642.57813] 419 [263.18359 265.13672 263.18359] 432 [386.23047 0 0 0 378.90625] 441 [325.19531 324.70703] 464 [972.16797] 473 [291.99219] ] /DW 0 >> endobj 43 0 obj << /Length 470 /Filter /FlateDecode >> stream x]0>nyv;Oz[܃Ut2? 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