Fractionated RT modulates the local TCR repertoire 2 Translational Relevance. Radiotherapy (RT) is well documented to be immunogenic; however, systemic anti-tumor immune responses outside of the irradiated tumor field, termed the "abscopal effect", are rare in patients. The lack of abscopal effect is poorly understood, particularly in the context of low-dose daily fractionated RT, the most common regimen used in clinical practice. We demonstrate that 5 daily fractions of 2 Gy induces a polyclonal T-cell response at the irradiation site which is dominated by the expansion of pre-existing T-cell clones. However, Conclusions:These data provide evidence that RT can enhance T-cell trafficking to locally-treated tumor sites and augment pre-existing anti-cancer T-cell responses with the capacity to mediate regression of out-of-field tumor lesions when delivered in combination with αPD-1 mAb therapy.

Background: The chemokine CXCL12 and its cognate receptor, CXCR4, have been implicated in numerous tumour types where expression promotes tumour growth, angiogenesis, metastasis and suppresses tumour immunity. Methods: Using a tissue microarray of 289 primary ovarian cancers coupled to a comprehensive database of clinicopathological variables, the expression of CXCL12 and CXCR4 was assessed by immunohistochemistry and its impact in terms of survival and clinicopathological variables was determined. Results: Patients whose tumours expressed high levels of CXCL12 had significantly poorer survival ( P =0.026) than patients whose tumours failed to produce this chemokine. Lack of CXCL12 expression within tumours was associated with a 51-month survival advantage for patients when compared with patients whose tumours expressed high levels of CXCL12. FIGO stage, adjuvant chemotherapy and the absence of macroscopic disease after surgery were all shown to predict prognosis independently of each other in this cohort of patients. CXCL12 was independently predictive of prognosis on multivariate analysis ( P =0.016). There was no correlation between CXCL12 and any clinicopathological variable. Conclusion: The chemokine CXCL12 is an independent predictor of poor survival in ovarian cancer. High expression of CXCL12 was seen in only 20% of the tumours, suggesting a role for anti-CXCL12/CXCR4 therapy in the management of these patients.

Allergic contact dermatitis (ACD) is driven by the activation and proliferation of allergen-specific memory T-lymphocytes and is currently diagnosed by patch testing with a selected panel of chemical allergens. The lymphocyte transformation test (LTT) can be used to monitor ex vivo T-lymphocyte responses to antigens, including contact allergens. The LTT is not viewed as being an alternative to patch testing, but it does seek to reflect experimentally skin sensitization to specific chemicals. The LTT is based on stimulation in vitro of antigendriven T-lymphocyte proliferation. That is, exposure in culture of primed memory T-lymphocytes to the relevant antigen delivered in an appropriate configuration will provoke a secondary response that reflects the acquisition of skin sensitization. The technical aspects of this test and the utility of the approach for investigation of immune responses to contact allergens in humans are reviewed here, with particular emphasis on further development and refinement of the protocol. An important potential application is that it may provide a basis for characterizing those aspects of T-lymphocyte responses to contact allergens that have the greatest influence on skin sensitizing potency and this will be considered in some detail.

MI-HSA is able to induce secondary responses in lymphocytes drawn from sensitized subjects, and provides a more effective source of antigen than free MI. Furthermore, individual donors show differential activity profiles with respect to T lymphocyte subsets.