Al for ImmunoTherapy of Cancer 2018, 6(Suppl 1):P495 Background Tumors recruit BMC for the tumor microenvironment and modulate BMCs [immunosuppressive tumor-associated macrophages (TAM), neutrophils (TAN), and myeloid derived suppressor cells (MDSC)] in tumor microenvironment (Schupp, Cellular Immunology, 2017; Ginhoux, Nat Rev Immunology, 2014). Predominantly immature BMCs are linked with poor prognosis (Bergenfelz, PLoS One, 2015; Toor, Cancer Immunol Immunother, 2017). An elevated Signal Regulatory Protein Beta Proteins web N-to-L Ratio (NLR) of NLR 5, and reduced L-to-M ratio (LMR) of three.2 are predictive of poor prognosis in cancer sufferers (pts) (Zhou; Nature, 2017; Sierzega; Ann Surg Onc, 2017). Chemotherapy (chemo) induced neutropenia (CIN) is mitigated with G-CSF for example pegfilgrastim (Peg). Plin can be a novel non-G-CSF small molecule, using a various mechanism of action for CIN (LSK inhibition reversal; Lloyd AACR, 2017). Plin (by IV) and Peg (by SC) are given as a single dose-per-cycle. In contrast to Peg, Plin is provided on the identical day of chemo, 30 minutes after chemo, vs 24 hours after chemo with Peg. Plin will not bring about bone pain, and has anti-cancer, immune-enhancing activity (Mohanlal, ASCO-SITC 2018). The Phase (Ph)two portion of Study BPI-2358-105 (NCT03P171 Corresponding author e mail: [email protected]) in NSCLC pts, compared Plin (at various doses; n=55) with Peg for the prevention of Docetaxel (Doc) CIN. Plin (20 mg/m2) and Peg are equally productive for the prevention of Doc CIN, in respect to frequency and duration of severe neutropenia (Blayney, ASCO 2018). Due to the fact Plin and Peg both enhance BMCs, we evaluated their respective immunosuppressive potential. Methods BMCs from cycle 1 of Ph2 study 105 was analyzed with either Plin (20 mg/m2; n=14) or Peg (six mg; n=14). BMCs, such as immature Ns ((pro)myelocytes and bands) were readily available via day (D) 15. Final results In contrast to Peg, Plin didn’t show NLR5 or LMR3 (Table beneath). N bands have been observed in 25 vs 0 of pts with Peg and Plin resp. (Pro)myelocytes were observed in 77 vs 14 of pts with Peg and Plin, resp (p0.001). Conclusions Peg, but not Plin generates a BMC profile with a predominant immunosuppressive phenotype, even though each are equally productive for the prevention of Doc CIN.P496 Innate and adaptive immune responses to metastatic colorectal cancer differ by sex and correlate with survival Anita Ray, PhD1, Robert Nofchissey, BS1, Sarah Adams, MD2, William Berry1, Katherine Morris, MD, FACS3 1 OUHSC, Oklahoma City, OK, USA; 2UNM, Albuquerque, NM, USA; 3 University of Oklahoma Stephenson Cancer Center, Oklahoma City, OK, USA Correspondence: Katherine Morris ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P496 Background Ladies with colorectal cancer (CRC) possess a survival advantage more than guys. The mechanism behind this is unclear. CRC is strongly PTPRK Proteins web influenced by the tumor immune microenvironment (TME), with many immune cell varieties and signaling pathways implicated in its initiation, progression, and metastasis. Moreover, murine models of sepsis have demonstrated elevated numbers of peritoneal leukocytes and elevated activation in females that correlate with improved survival [1,2]. Macrophages are vital participants inside the CRC TME and can drive pro- and anti- inflammatory shifts. We hypothesized that the immune CRC TME is sex-dependent and contributes to enhanced survival in females. Techniques Male and female C57/Bl6 mice have been injected with 105 MC38 cells intraperitoneally.
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