Sherzer identifies discourse as “the nexus, the actual and concrete expression of the language‐culture‐society relationship” (1987:296), and offers the term “heightened discourse” for those moments in which language and culture (e)merge in language use. In this paper I use dialogic syntax (Du Bois 2014) to pinpoint moments of heightened discourse in everyday conversation carried out in Tojolab'al. After illustrating the basic dialogic syntax units of diagraphs and processes of resonance with Tojol‐ab'al examples, I then analyze two segments of speech play in Tojol‐ab'al, which abound in repetitions and resonances. Diagraphs of segments of these interactions highlight the parallel structure of the talk, which centers on culturally important topics. The dense resonance of repetition and parallelism in these segments reveal them to be heightened discourse. Resonance and heightened discourse are both characterized by an exuberant level of engagement among interlocutors.

BackgroundGlypican-3 (GPC-3) is an oncofetal protein that is highly expressed in various solid tumors including hepatocellular carcinoma (HCC) but is rarely expressed in healthy adult tissues and serves as a therapeutic target of interest. Autologous αβ chimeric antigen receptor (CAR) T cell therapy has established clinical benefit in hematologic malignancies but limited success in solid tumors due to numerous challenges including poor T cell homing, heterogenous antigen expression, and hostile tumor microenvironments.1 These challenges may be overcome by the Vδ1 subset of gamma delta T cells due to their natural peripheral tissue tropism and ability to recognize and kill tumor cells through MHC-independent antigens upregulated under stress.2 Allogeneic Vδ1 T cells engineered with CARs can have enhanced intrinsic antitumor activity and overcome challenges of allogeneic αβ T cells, including graft-versus-host disease (GvHD). Here, we describe the first preclinical evaluation of ADI-002, a next-generation allogeneic CAR Vδ1 T cell therapy targeting GPC-3 and armored with IL-15, for the treatment of solid tumors.MethodsVδ1 T cells were expanded from healthy donor PBMCs and transduced to express a 4–1BB/CD3z CAR against GPC-3 that encodes constitutively-secreted IL-15 (sIL-15), which we hypothesized could sustain proliferation and antitumor activity of intratumoral GPC-3.CAR Vδ1 T cells. In vitro characterization included co-culture with HCC targets expressing high (HepG2) and low (PLC/PRF/5) GPC-3, phenotypic analysis by flow cytometry, and cytokine production by multiplexed immunoassay. For in vivo assessment, immunodeficient NSG mice were subcutaneously injected with HepG2 tumor cells and treated with a single dose of GPC-3.CAR Vδ1 T cells. Tissues were harvested 7 days post transfer and analyzed for Vδ1 T cell tissue homing and proliferation, or at study end and analyzed for GvHD by immunohistochemistry.ResultsGPC-3.sIL-15.CAR Vδ1 T cells expanded over 10,000-fold and routinely reached >80% purity. Expanded Vδ1 T cells showed a primarily naïve-like phenotype (CD45RA+CD27+) with minimal exhaustion receptor expression and displayed robust proliferation, cytokine production, and cytotoxic activity against HCC cell lines in vitro. In vivo, GPC-3.sIL-15.CAR Vδ1 T cells primarily accumulated and proliferated in tumors, and a single dose could efficiently control tumor burden without causing GvHD. When compared to GPC-3.CAR Vδ1 T cells lacking sIL-15, GPC-3.sIL-15.CAR Vδ1 T cells displayed greater tumor-specific proliferation that resulted in enhanced tumor control (figure 1).Abstract 119 Figure 1In vivo antitumor efficacy in a subcutaneous HepG2 tumor model in NSG miceConclusionsExpanded Vδ1 T cells engineered with GPC-3.CAR and sIL-15 represent a promising approach for safe and effective off-the-shelf treatment of HCC and support further investigation in the clinical setting.ReferencesLabanieh L, Majzner RG, Mackall CL. Programming CAR-T cells to kill cancer. Nat Biomed Eng 2018;2(6):377–91.Sebestyen Z, Prinz I, Déchanet-Merville J, Silva-Santos B, Kuball J. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov 2020;19(3):169–84.Ethics ApprovalAll mouse experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals and followed all institutional and national guidelines and after appropriate approvals.

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This pilot study examines texts from three generations of speakers of Tojol-ab’al, a Mayan language that has been in long-term contact with Spanish, to determine the influence from Spanish on Tojol-ab’al narrative discourse. Discourse markers borrowed from Spanish and those indigenous to Tojol-ab’al are examined to determine discourse structure. Discourse markers borrowed from Spanish appear frequently even in the speech of the oldest, monolingual generation. Although the youngest generation uses many more words (nouns, verbs) borrowed from Spanish than do the earlier generations, narrative discourse structure, as indicated by the use of both borrowed and indigenous discourse markers, remains substantially the same through time.