Natural immunity to cancer in humans

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The evolution of cancer reflects intricate cellular and molecular interactions of tumor cells with the tumor microenvironment. Novel systems biology approaches are emerging to analyze the complex interaction between tumors and host-immune response in humans. The opposing host-protective and tumor-promoting roles of the immune system reflect the disparate effects of immunity on tumorigenesis. Global analysis of tumor microenvironment showed that a strong adaptive immune reaction within primary human tumors reduced the risk of relapse events. Recent advances support the existence of immunosurveillance in human cancer. The major role of the intratumoral immune reaction could advance our understanding of tumor evolution and have important consequences in clinical practice.

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Advocacy for integrative cancer immunology

The tumor develops in a complex microenvironment comprising fibroblasts, endothelial cells, blood vessels, lymph vessels, immune cells, cytokines, chemokines, and products of cellular metabolism. By its components, the tumor microenvironment influences the growth of the tumor and its capacity to progress and to form metastases. In particular, the evolution of cancer reflects complex cellular and molecular interactions of the tumor with the immune system of the host [1]. The characterization of

Immunosurveillance despite inflammation

In the literature there is an apparent conflict between the opposing host-protective and tumor-promoting roles of the immune system. Although this dichotomous view may facilitate the interpretation of data, maybe it is a too simplistic approach. We propose that the host-protecting action and inflammation can be overlapping immune responses, and that an orchestrated immune response against a developing tumor will contain different types of effector cells and molecules with co-existing

Lessons from human cancer analysis

In contrast to infiltration of cells responsible for chronic inflammation, the presence of high numbers of lymphocytes, especially T cells, has been reported as being of good prognosis in many cancer types: melanoma, non-Hodgkin lymphoma, non-small cell lung cancer, breast, ovarian, head, neck, esophagus, urothelial, and colorectal cancer [26, 32, 33•, 34, 35, 36, 37, 38, 39•, 40]. Regulatory T cells (Tregs) may modulate the immune function. However, increased tumor Tregs have been associated

The strongest prognostic factor for recurrence and overall survival: the immune contexture

Histopathological analysis of colorectal cancers shows that many tumors are infiltrated in variable quantities by inflammatory and lymphocytic cells. A closer look reveals that the latter are not randomly distributed, but rather seem to be organized as more or less dense infiltrations in different regions, that is the center of the tumor (CT) and at the forefront region of the tumor within the colonic mucosa, so called, the invasive margin (IM) of the tumor. We have extensively analyzed the

Global analysis of the intratumoral immune reaction: a breakthrough for patient prognosis

Analysis of immune cell densities was performed in regional lymph node metastases from Dukes’ stage C colorectal cancer. In patients with or without adjuvant radio/chemotherapy, the presence high numbers of CD8+ and CD45R0+ cells in regional lymph node correlated with increased survival time [52]. Furthermore, sentinel node from primary tumor and metastasis showed characteristics of tumor-reactive lymphocytes [53]. However, evaluation of T-cell subpopulations in lymph node is difficult in

A long-term memory against cancer?

Our results suggest that once human colorectal cancers become clinically detectable, the adaptive immune response plays a role in preventing tumor recurrence. Despite immunoediting mechanisms, the beneficial effect of the adaptive immunity may persist throughout tumor progression (stages II and III). Intratumoral T cells could modify tumor stroma or tumor cells in ways that attenuate their metastatic potential. The absence of microscopic evidence of early metastatic invasiveness within

Conclusions

Systems biology and biomolecular network reconstruction will be powerful approaches to uncover mechanisms associated with tumor progression and tumor recurrence. Integrative analyses evaluating the immune infiltrate in human cancers are of major importance. Compared to the immune contexture, no tumor parameter associated with survival has been reported to achieve a similarly high level of significance in colorectal cancer. This suggests that markers of the oncogenic process are closely

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We acknowledge all the scientists who made contributions to the area of research reviewed here that were not cited due to space constraints. The work performed in our laboratory was supported by grants from the Association pour la Recherche sur le Cancer (ARC), the National Cancer Institute (INCa), the Canceropole Ile de France, Ville de Paris, Inserm, and the European Commission (7FP, Geninca Consortium, grant number 202230).

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