Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host's response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14-15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual's recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4-5, 2019.

A prospective, multicenter study of complementary/alternative medicine (CAM) utilization during definitive radiation for breast cancer.

PURPOSE: Although complementary and alternative medicine (CAM) utilization in breast cancer patients is reported to be high, there are few data on CAM practices in breast patients specifically during radiation. This prospective, multi-institutional study was conducted to define CAM utilization in breast cancer during definitive radiation. MATERIALS/METHODS: A validated CAM instrument with a self-skin assessment was administered to 360 Stage 0-III breast cancer patients from 5 centers during the last week of radiation. All data were analyzed to detect significant differences between users/nonusers. RESULTS: CAM usage was reported in 54% of the study cohort (n=194/360). Of CAM users, 71% reported activity-based CAM (eg, Reiki, meditation), 26% topical CAM, and 45% oral CAM. Only 16% received advice/counseling from naturopathic/homeopathic/medical professionals before initiating CAM. CAM use significantly correlated with higher education level (P<.001), inversely correlated with concomitant hormone/radiation therapy use (P=.010), with a trend toward greater use in younger patients (P=.066). On multivariate analysis, level of education (OR: 6.821, 95% CI: 2.307-20.168, P<.001) and hormones/radiation therapy (OR: 0.573, 95% CI: 0.347-0.949, P=.031) independently predicted for CAM use. Significantly lower skin toxicity scores were reported in CAM users vs nonusers, respectively (mild: 34% vs 25%, severe: 17% vs 29%, P=.017). CONCLUSION: This is the first prospective study to assess CAM practices in breast patients during radiation, with definition of these practices as the first step for future investigation of CAM/radiation interactions. These results should alert radiation oncologists that a large percentage of breast cancer patients use CAM during radiation without disclosure or consideration for potential interactions, and should encourage increased awareness, communication, and documentation of CAM practices in patients undergoing radiation treatment for breast cancer.