FIX latex errors

tex/thesis.tex

@@ -81,6 +81,9 @@
   palindromic repeats}
 \newacronym{mtt}{MTT}{3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide}
 \newacronym{bmi}{BMI}{body mass index}
+\newacronym{a2b1}{A2B1}{integrin $\upalpha$1$\upbeta$1}
+\newacronym{a2b2}{A2B2}{integrin $\upalpha$1$\upbeta$2}
+\newacronym{til}{TIL}{tumor infiltrating lymphocytes}
 
 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
 % SI units for uber nerds
@@ -1403,27 +1406,27 @@ subsets to be included in CAR T cell therapy given a disease state.
 % the signaling and why this might matter
 There are several plausible explanations for the observed phenotypic differences
 between beads and DMSs. First, the DMSs are composed of a collagen derivative
-(gelatin); collagen has been shown to costimulate activated T cells via α1β1 and
-α2β1 integrins, leading to enhanced proliferation, increased IFNγ production,
-and upregulated CD25 (IL2Rα) surface expression8,10,11,41,42. Second, there is
-evidence that providing a larger contact area for T cell activation provides
-greater stimulation16,43; the DMSs have a rougher interface than the 5 µm
-magnetic beads, and thus could facilitate these larger contact areas. Third, the
-DMSs may allow the T cells to cluster more densely compared to beads, as
-evidenced by the large clusters on the outside of the DMSs (Figure 1f) as well
-as the significant fraction of DMSs found within their interiors (Supplemental
-Figure 2a and b). This may alter the local cytokine environment and trigger
-different signaling pathways. Particularly, IL15 and IL21 are secreted by T
-cells and known to drive memory phenotype44–46. We noted that the IL15 and IL21
-concentration was higher in a majority of samples when comparing beads and DMSs
-across multiple timepoints (Supplemental Figure 18) in addition to many other
-cytokines. IL15 and IL21 are added exogenously to T cell cultures to enhance
-memory frequency,45,47 and our data here suggest that the DMSs are better at
-naturally producing these cytokines and limiting this need. Furthermore, IL15
-unique signals in a trans manner in which IL15 is presented on IL15R to
-neighboring cells48. The higher cell density in the DMS cultures would lead to
-more of these trans interactions, and therefore upregulate the IL15 pathway and
-lead to more memory T cells.
+(gelatin); collagen has been shown to costimulate activated T cells via
+\gls{a2b1} and \gls{a2b2}, leading to enhanced proliferation, increased
+IFN$\upgamma$ production, and upregulated CD25 (IL2R$\upalpha$) surface
+expression8,10,11,41,42. Second, there is evidence that providing a larger
+contact area for T cell activation provides greater stimulation16,43; the DMSs
+have a rougher interface than the 5 µm magnetic beads, and thus could facilitate
+these larger contact areas. Third, the DMSs may allow the T cells to cluster
+more densely compared to beads, as evidenced by the large clusters on the
+outside of the DMSs (Figure 1f) as well as the significant fraction of DMSs
+found within their interiors (Supplemental Figure 2a and b). This may alter the
+local cytokine environment and trigger different signaling pathways.
+Particularly, IL15 and IL21 are secreted by T cells and known to drive memory
+phenotype44–46. We noted that the IL15 and IL21 concentration was higher in a
+majority of samples when comparing beads and DMSs across multiple timepoints
+(Supplemental Figure 18) in addition to many other cytokines. IL15 and IL21 are
+added exogenously to T cell cultures to enhance memory frequency,45,47 and our
+data here suggest that the DMSs are better at naturally producing these
+cytokines and limiting this need. Furthermore, IL15 unique signals in a trans
+manner in which IL15 is presented on IL15R to neighboring cells48. The higher
+cell density in the DMS cultures would lead to more of these trans interactions,
+and therefore upregulate the IL15 pathway and lead to more memory T cells.
 
 % TODO this mentions the DOE which is in the next aim
 When analyzing all our experiments comprehensively using causal inference, we
@@ -1531,15 +1534,15 @@ manufacturing companies.
 Finally, while we have demonstrated the DMS system in the context of CAR T
 cells, this method can theoretically be applied to any T cell immunotherapy
 which responds to anti-CD3/CD28 mAb and cytokine stimulation. These include
-tumor infiltrating lymphocytes (TILs), virus-specific T cells (VSTs), T cells
-engineered to express γδTCR (TEGs), γδ T cells, T cells with transduced-TCR, and
-CAR-TCR T cells53–58. Similar to CD19-CARs used in liquid tumors, these T cell
-immunotherapies would similarly benefit from the increased proliferative
-capacity, metabolic fitness, migration, and engraftment potential characteristic
-of naïve and memory phenotypes59–61. Indeed, since these T cell immunotherapies
-are activated and expanded with either soluble mAbs or bead-immobilized mAbs,
-our system will likely serve as a drop-in substitution to provide these
-benefits.
+\glspl{til}, virus-specific T cells (VSTs), T cells engineered to express
+$\upgamma\updelta$TCR (TEGs), $\upgamma\updelta$ T cells, T cells with
+transduced-TCR, and CAR-TCR T cells53–58. Similar to CD19-CARs used in liquid
+tumors, these T cell immunotherapies would similarly benefit from the increased
+proliferative capacity, metabolic fitness, migration, and engraftment potential
+characteristic of naïve and memory phenotypes59–61. Indeed, since these T cell
+immunotherapies are activated and expanded with either soluble mAbs or
+bead-immobilized mAbs, our system will likely serve as a drop-in substitution to
+provide these benefits.
 
 \chapter{aim 2}\label{aim2}