Jing Wang

The question as to why some hosts can eradicate their tumors while others succumb to tumor‐progression remains unanswered. Here, a provocative concept is proposed that intrinsic differences in the T cell receptor (TCR) repertoire of individuals may influence the outcome of anti‐tumor immunity by affecting the frequency and/or variety of tumor‐reactive CD8 and/or CD4 tumor‐infiltrating lymphocytes. This idea implicates that the TCR repertoire in a given patient might not provide sufficiently different TCR clones that can recognize tumor antigens, namely, “a hole in the TCR repertoire” might exist. This idea may provide a novel perspective to further dissect the mechanisms underlying heterogeneous anti‐tumor immune responses in different hosts. Besides tumor‐intrinsic heterogeneity and host microbiome, the various factors that may constantly shape the dynamic TCR repertoire are also discussed. Elucidating mechanistic differences in different individuals’ immune systems will allow to better harness immune system to design new personalized cancer immunotherapy.

Despite research supporting the efficacy of family therapy for adolescent depression, little research has been done to clarify the therapeutic variables that Chinese families with depressed adolescents consider helpful in family therapy. This study explored Chinese depressed adolescents’ and their parents’ perceptions of the factors promoting improvement in family therapy. Twelve Chinese families with one adolescent child fulfilling the criteria for major depressive disorder were recruited. A total of 134 family therapy sessions were conducted by 4 therapists. After therapy, semi-structured interviews about the clients’ perceptions of the helpful and effective aspects of therapy were conducted. Thematic analysis was used to analyze the transcribed dialogues. Five overarching themes emerged: factors supporting therapeutic alliance formation, the therapist’s systemic attitude, systemic therapy direction, effective systemic therapy techniques and strategies for dealing with current issues. A trustworthy therapy alliance with a competent and supportive therapist helped depressed adolescents improve by facilitating the expression of their emotions; exploring family interactions, beliefs and emotion flows related to their symptoms; promoting their self-development; and activating their resources. The families valued the respectfulness of the therapists and their collaborative and nonauthoritative approach. Adolescents’ academic difficulties and crises received special attention. The possible clinical implementations of our findings in the design of family therapy strategies for depressed Chinese adolescents are discussed.

Dynamic modulation of cell adhesion is integral to a wide range of biological processes. The small guanosine triphosphatase Rap1 is an important regulator of cell - cell and cell - matrix adhesions. We show here that induced expression of activated Abl tyrosine kinase reduces Rap1-GTP levels through phosphorylation of Tyr221 of CrkII, which disrupts interaction of CrkII with C3G, a guanine nucleotide exchange factor for Rap1. Abl-dependent down-regulation of Rap1-GTP causes cell rounding and detachment only when the Rho - ROCK1 pathway is also activated, for example, by lysophosphatidic acid. During ephrin-A1 - induced retraction of PC3 prostate cancer cells, we show that endogenous Abl is activated and disrupts the CrkII - C3G complex to reduce Rap1-GTP. Interestingly, ephrin-A1 - induced PC3 cell retraction also requires LPA, which stimulates Rho to a much higher level than that is activated by ephrin-A1. Our results establish Rap1 as another downstream target of the Abl - CrkII signaling module and show that Abl - CrkII collaborates with Rho - ROCK1 to stimulate cell retraction. © 2008 Huang et al.