Integrating the patients' voice in designing and delivering a research study: The Yorkshire Cancer Research funded PREHABS study's experience.

INTRODUCTION: Engaging with patients when designing a clinical or research project is beneficial; feedback from the intended audience provides invaluable insight form the patients' perspective. Working with patients can result in developing successful research grants and interventions. The benefit of including the voice of the patient in the Yorkshire Cancer Research funded PREHABS study is described in this article. METHODS: Patients were included in the PREHABS study from inception to completion. The Theory of Change methodology was used to provide a framework to implement patient feedback to refine the study intervention. RESULTS: In total, 69 patients engaged with the PREHABS project. Two patients were recruited as co-applicants on the grant and were members on the Trial Management Group. Six patients attended the pre application workshop and provided feedback on their lived experiences of being a lung cancer patient. Commentary from the patients influenced the interventions selected and the design of the prehabs study. Following ethical approval (21/EE/0048) and informed written consent, 61 patients were recruited into the PREHABS study between October 2021 and November 2022. The breakdown of recruited patients was 19 males: mean age 69.1 years (SD 8.91) and 41 females; mean age 74.9 years (SD 8.9). CONCLUSION: It is practicable and beneficial to include patients at all stages of designing and delivering a research study. Patient feedback can help refine the study interventions to allow for maximum acceptance, recruitment and retention. IMPLICATIONS FOR PRACTICE: Including patients in the design of radiotherapy research studies can provide invaluable insight that can support the selection and delivery of interventions that are acceptable to the patient cohort.

Cell populations in leucocyte adherence inhibition: requirement for T lymphocytes with IgG Fc receptors.

The subset identity of T lymphocytes participating in the leucocyte adherence inhibition (LAI) reaction was investigated. Humans were immunized with keyhole limpet haemocyanin (KLH) and their cellular immunity was tested by means of the haemocytometer variant of the LAI method. Their lymphocytes were fractionated by rosetting methods employing neuraminidase-treated sheep erythrocytes and IgG- or IgM-coated ox erythrocytes. The T lymphocytes rosetted by IgG-coated ox cells (T gamma) reacted with KLH to give specific LAI reactions. Non-T gamma cells failed to react. The T gamma cells released a lymphokine which caused an LAI reaction of T lymphocytes from non-immunized donors. Immune non-T gamma cells, when incubated with KLH yielded inactive supernates. The normal cells which gave positive LAI responses to the lymphokine also proved to belong exclusively to the T gamma subclass. Cells positively selected with IgM-coated ox cells (T micro) were inactive while the non-T micro lymphocytes behaved like the T gamma cells. It was shown that the activity was confined to the T gamma subset throughout the time course of a primary immune response. Thus, LAI reactivity appears to be a property of a very small subclass of lymphocytes which communicate with each other by means of a soluble factor.

Immunological basis of close-contact sensitization to osteosarcoma.

Normal persons with a history of close contact with cancer patients often given positive responses in tests for specific tumor immunity. The present study was designed to establish the immunological relevance of such reactivity. Leukocyte adherence inhibition analysis was used to test responses of osteosarcoma (OS)-positive donors to extracts of OS. The test system proved highly specific in that positive leukocyte adherence inhibition responses were detected in 35 of 39 OS patients while only 6 to 7% of the controls were positive. Thus, the test system appears useful in the detection of OS. Two persons reactive presumably because of exposure to OS tissue gave booster-like leukocyte adherence inhibition responses on each reexposure. Reactivity was abrogated by treatment of their leukocytes with a goat anti-T-cell immunoglobulin G. Thus, the reactivity of cells from normal donors exposed to OS probably has an immunological basis, since the test system was highly specific, reflected anamnestic reactivity, and depended on lymphocytes (probably thymus dependent). These findings suggest that an OS-associated antigen can be transmitted horizontally, but the relation of immunity to risk remains obscure.

Antigenic specificity and cellular mechanisms in leukocyte adherence inhibition analysis of immunity to simple proteins and hapten-protein conjugates.

The hemacytometer leukocyte adherence inhibition (LAI) assay was investigated with respect to immunological relevance, specificity, and cellular mechanisms. Humans were immunized to keyhole limpet hemocyanin, and rats were immunized to dinitrophenyl-bovine gamma-globulin. LAI analysis disclosed classic patterns of immune response kinetics. The LAI response was dose dependent in vitro with no inhibition at relatively high antigen doses. In vitro specificity in rats was restricted to the immunizing conjugate. Cells forming spontaneous E-rosettes were required for LAI reactions. Lymphokine production required the presence of E-rosette-forming cells. E-rosette-forming cells from normal donors lost adherence in the presence of lymphokine. The requirement for T-lymphocytes was confirmed in a human osteosarcoma system using independent criteria. Thus, the hemacytometer LAI depends upon T-lymphocyte collaboration via a lymphokine. It should be distinguished from the tube and microplate variants of LAI analysis because these appear to depend upon different mechanisms.

Leukocyte-adherence inhibition: a specific assay of cell-mediated immunity dependent on lymphokine-mediated collaboration between T lymphocytes.

The leukocyte-adherence inhibition (LAI) assay was studied to determine its immunologic relevance and identify the cell populations on which it depends. Two systems were employed: peripheral blood leukocytes from humans immunized with KLH, and lymph node cells from rats immunized with DNP-BCG. In both cases, LAI responses appeared about 3 to 4 days after immunization, reached a peak about 3 to 4 weeks later, and diminished thereafter. Reimmunization resulted in a booster-like response. LAI analysis in both systems showed dose-response dependency. Responses could be elicited only with the immunizing antigen. Virtual depletion of phagocytic cells had no effect on the response. E-rosette-forming cells gave an excellent response to KLH and also produced an active supernatant (lymphokine). Cells not forming spontaneous E-rosettes were inactive and could not produce active supernatants. Only those nonimmune cells that formed E-rosettes could respond to active supernatants. Thus, the LAI response is a specific indicator of cell-mediated immunity. T lymphocytes probably are required both at the antigen-reactive stage and at the stage of responding to the T cell-dependent lymphokine.

Specific responsiveness of leukocytes to soluble extracts of human tumors.

The leukocyte adherence inhibition (LAI) method was studied with respect to its specificity in detecting responses to extracts of tumor tissues or normal lymphocytes. Responses of cells from normal persons were within 10% of each other whether incubation was carried out with culture medium alone or with any of the extracts. The same was true of cells from 78 cancer patients unless the cells were incubated with extracts of the same histologic type as their own. In the latter case, statistically significant responses occurred in 95% of the 110 analyses done. Negative responses were given by cells from 14 patients tentatively diagnosed as having breast carcinoma but whose lesions later proved benign. There was one positive response inconsistent with the diagnosis. Of 29 normal individuals known to have been exposed to tumors or tumor extracts, 11 responded positively and specifically to the relevant tumor extract. Cells from 12 of 30 multiparous female breast-cancer patients responded to extracts of pooled normal lymphocytes. The results establish that the LAI analysis is an extremely specific means of detecting systemic responses to malignant diseases. In addition, analyses have proven positive in 95% of the cases studied.